Conformable therapeutic shield for vision and pain

ABSTRACT

A conformable covering comprises an outer portion with rigidity to resist movement on the cornea and an inner portion to contact the cornea and provide an environment for epithelial regeneration. The inner portion of the covering can be configured in many ways so as to conform at least partially to an ablated stromal surface so as to correct vision. The conformable inner portion may have at least some rigidity so as to smooth the epithelium such that the epithelium regenerates rapidly and is guided with the covering so as to form a smooth layer for vision. The inner portion may comprise an amount of rigidity within a range from about 1×10−4 Pa*m3 to about 5×10−4 Pa*m3 so as to deflect and conform at least partially to the ablated cornea and smooth an inner portion of the ablation with an amount of pressure when deflected.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present PCT application claims priority to the following U.S.provisional applications: U.S. App. Ser. No. 61/279,613 filed 23 Oct.2009, entitled “Conformable Therapeutic Shield for Vision and Pain”(attorney docket no. 26322A-000200US); U.S. App. Ser. No. 61/322,206filed 8 Apr. 2010, entitled “Conformable Therapeutic Shield for Visionand Pain” (attorney docket no. 26322A-000210US); the full disclosures ofwhich are incorporated herein by reference.

STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSOREDRESEARCH AND DEVELOPMENT

Not Applicable

BACKGROUND OF THE INVENTION

The present invention is generally directed to visual rehabilitation andtreatment of pain for patients with epithelial defects on the cornea ofthe eye. Although specific reference is made to epithelial defectsfollowing photorefractive keratectomy, embodiments of the presentinvention can be used to treat epithelial defects from other causes, forexample corneal abrasions, trauma, keratoconus, penetrating keratoplastyand dystrophies.

The eye includes several tissues that allow patients to see. The corneaof the eye is an anterior tissue of the eye that is clear in healthyeyes and refracts light so as to form an image on the retina. The retinais a posterior tissue of the eye that senses light from the image formedthereon and transmits signals from the image to the brain. The corneaincludes an outer layer of tissue, the epithelium, which protects theunderlying tissues of the cornea, such as Bowman's membrane, the stromaand nerve fibers that extend into the stroma and Bowman's. The healthyeye includes a tear film disposed over the epithelium. The tear film cansmooth small irregularities of the epithelium so as to provide anoptically smooth surface. The tear film is shaped substantially by theshape of the underlying epithelium, stroma, and Bowman's membrane, ifpresent. The tear film comprises a liquid that is mostly water and doesinclude additional components, such as mucoids and lipids. The manynerve fibers of the cornea provide sensation to promote blinking thatcan cover the cornea with the tear film. The never fibers also sensepain so that one will normally avoid trauma to the cornea and also avoiddirect contact of an object to the cornea so as to protect thisimportant tissue.

In the healthy cornea, the proper amount of hydration of the cornea,sometimes referred to as dehydration of the cornea, is maintained suchthat the cornea remains clear. The cornea includes a posteriorendothelial layer that pumps water from the cornea into the adjacentanterior chamber. The epithelium minimizes flow of water from the tearliquid into the cornea, such that the corneal stroma can be maintainedwith the proper amount of hydration with endothelial pumping. Theendothelial pumping of water from the cornea to maintain the properhydration and thickness of the eye is often referred to asdeturgescence.

In patients with epithelial defects, the barrier function of theepithelium is compromised, such that water can enter the cornea throughthe epithelial defect so as to cause swelling of the corneal stroma. Asa result, excessive hydration of the cornea may occur in eyes withepithelial defects. In some instances, excessive hydration that swellsthe corneal stroma can result in light scattering, or haze, such that animage seen by a patient is degraded. The scattering of light by thecorneal stroma can be seen with a slit lamp examination to diagnose thepatient, and is sometimes referred to as corneal haze. In addition topotentially causing excess hydration of the cornea, an epithelial defectcan expose the nerve fibers of the cornea such that the patient feelspain.

Several known techniques exist to treat corneal epithelial defects,including bandage therapeutic lenses, non-steroidal anti-inflammatories(hereinafter NSAIDS), steroids, antibiotics and analgesics. These knowntechniques may be somewhat effective in reducing symptoms associatedwith the epithelial defect. However, many of these known techniques maynot provide a barrier to water entry into the corneal stroma, such thatthe cornea may swell with water and may affect patient vision in atleast some instances. For example, a bandage therapeutic lens may beplaced over the epithelial defect to cover and protect the cornealtissues under the defect, such as the corneal stroma and nerve fibers.However, in at least some instances the bandage therapeutic lens may notprevent water of the tear from leaking through the epithelial defectinto the stroma. Also, a bandage therapeutic lens may slide over theepithelial defect when positioned on the eye in at least some instances,potentially decreasing the therapeutic benefit when the lens slidesalong the delicate underlying tissue, for example when a patient blinks.

Work in relation to embodiments of the present invention suggests thatat least some of the known therapeutic bandage lenses used to treatepithelial defects may actually contribute to corneal edema and pain inat least some instances. At least some of the current bandage lenses mayprovide less oxygen than would be ideal, and decreased oxygen to thecornea may be related pain and corneal edema in at least some instances.Also, in at least some instances, bandage lenses may be fit loosely onthe cornea, such that water can go around the bandage lens and maypenetrate the stroma through the epithelial defect.

As the post-ablation cornea may have a complex shape, many of the priorcommercially available lenses may not fit the ablated cornea as well aswould be ideal, and in at least some instances fitting of lenses can betime consuming and awkward. Commercially available contact lenses havinga rigid central RGP portion and a soft peripheral skirt can be difficultand/or time consuming to fit to the ablated cornea and may not fit verywell in at least some instances. The ablated cornea may comprise anabrupt change in curvature near the edge of the ablation, and in atleast some instances it can be difficult to fit such lenses near theedge of the ablation. Also, at least some of the commercially availablecontact lenses may not be suitable for extended wear and may be removedeach day which can be awkward for a patient.

Although anesthetics such as lidocaine and proparacaine may reduce pain,the overuse of these treatments can delay regeneration of the epithelialtissue over the defect, such that the defect may last longer.Consequently many people with epithelial defects may feel pain and havedegraded vision while the epithelial defect heals.

Many people elect to undergo laser vision correction surgery to treatrefractive error of the eye, such as near sightedness. With one form ofthis surgery known as photorefractive keratectomy (hereinafter “PRK”), alarge area of the epithelium is removed, for example a 6 to 9 mm area.Following ablation of the underlying tissues such as the corneal stromaand/or Bowman's membrane, the epithelium grows back over the ablatedzone and the de-epithelialized area to cover the area where theepithelium was removed. This re-growth of the epithelium can take threeto four days, and at least some of the patients who undergo this surgerymay feel pain. In addition, the epithelium may be somewhat irregularwhile growing back over the corneal stroma, and the irregularities maydegrade patient vision in at least some instances. Further, work inrelation to embodiments of the present invention suggests that anteriorstromal edema, ablated surface irregularities and necrotic cells in theablated surface area may decrease vision in some instances. Therefore,improved treatment of epithelial defects may result in improved patientcomfort and vision following PRK, and possibly other surgeries thatremove the corneal epithelium.

In light of the above, it would be desirable to provide improvedtreatments for epithelial defects of the cornea, such as epithelialdefects following PRK. Ideally, these treatments would avoid at leastsome of the deficiencies of known techniques while providing improvedpatient comfort and/or vision while the epithelial defect heals.

BRIEF SUMMARY OF THE INVENTION

Embodiments of the present invention provide an improved covering totreat an eye having an epithelial defect, for example an epithelialdefect subsequent to refractive surgery such as PRK. The covering canimprove regeneration of the epithelium, such that the epithelium canregenerate smoothly and rapidly. The covering may be configured in manyways to encourage regeneration of the epithelium, can resist movementwhen placed on the eye, and may seal the cornea to restoredeturgescence, so as decrease irregularities of the cornea and improvevision. The covering may comprise an inner portion having a modulus anda thickness so as to conform at least partially to the ablated stromalsurface and so as to smooth irregularities of the epithelium and ablatedstroma, such that the patient can receive the optical benefit of theablation. The covering may comprise an outer portion that can contactthe epithelium or the conjunctiva so as to resist movement and in manyembodiments so as to seal the covering to decrease swelling of thecornea. The outer portion can be configured in many ways to contact thecornea or the conjunctiva so as to resist movement and in manyembodiments seal the cornea. The outer portion may extend to at least anouter portion of the cornea and may extend to at least the limbus andbeyond the cornea so as to contact the conjunctiva and couple to thesclera so as to resist movement.

The inner portion of the covering can be configured in many ways so asto conform at least partially to an ablated stromal surface so as tocorrect vision. As the inner portion can conform at least partially tothe ablated surface, the patient can receive the benefit of the ablationprofile that corrects vision. The conformable inner portion may have atleast some rigidity so as to smooth the epithelium such that theepithelium regenerates rapidly and is guided with the covering so as toform a smooth layer for vision. The inner portion may comprise a modulusand a thickness corresponding to an amount of rigidity so as to providepressure on the cornea and smooth irregularities when the inner portionis deflected and conforms at least partially to the cornea. The innerportion may comprise an amount of rigidity within a range from about1×10⁻⁴ Pa*m³ to about 5×10⁻⁴ Pa*m³ so as to deflect and conform at leastpartially to the ablated cornea and smooth an inner portion of theablation with pressure when deflected. The inner portion may comprise amodulus within a range from about 1 MPa to 35 MPa, for example from 4MPa to about 20 MPa, and may conform at least partially to the ablatedsurface and smooth corneal irregularities such as stromal and epithelialirregularities. The covering having the inner portion configured toconform at least partially to the ablated stroma can fit many sizes andshapes of the cornea very effectively such that the covering can beeasier for a practitioner to fit to the patient and provide a betterfit. The inner portion can provide an environment to promote epithelialregeneration and guide regeneration of the epithelium along the coveringand ablated surface. The covering may comprise a material having highoxygen permeability, for example silicone, with a wettable coatingdisposed on at least an upper surface of the covering to inhibitcoupling of the covering the eyelid and improve adherence of thecovering to the epithelium or the conjunctiva.

In a first aspect, embodiments of the present invention provide, acovering to treat an eye of a patient, in which the eye has anepithelium with a defect and an ablated stroma. The covering comprisesan inner portion comprising an inner rigidity to contact the stroma, andan outer portion comprising an outer rigidity to define an enclosurewith the inner portion and the ablated stroma to promote growth of theepithelium.

In many embodiments, the enclosure provides an environment to promotegrowth of the epithelium over the defect within about 2 days ofablation.

In many embodiments, the enclosure comprises a terrarium to promotegrowth of the epithelium over a defect. For example, the enclosure maycomprise a terrarium to promote growth of the epithelium over a defectat least about 6 mm across within about 2 days of a PRK ablation.

In many embodiments, the enclosure comprises a chamber to promote growthof the epithelium over the defect within about 2 days of ablation.

In many embodiments, the inner portion comprises an oxygen permeabilityDk parameter of at least about 300. For example, the inner portion maycomprise an oxygen permeability Dk parameter of at least about 400, forexample, at least about 450.

In many embodiments, the inner portion comprises a wettable surface onat least an upper surface and wherein the inner portion comprises anoxygen permeability Dk parameter of at least about 300. The innerportion may comprise a wettable surface on at least an upper surface,and the inner portion may comprise an oxygen permeability Dk parameterof at least about 400. The inner portion may comprises a wettablesurface on at least an upper surface and the inner portion may comprisean oxygen permeability Dk parameter of at least about 450.

In many embodiments, the outer rigidity comprises a rigidity to indentthe epithelium when the outer portion is adhered to the cornea.

In many embodiments, the outer rigidity comprises a rigidity to conformto a boundary of the epithelium with the epithelial defect and to indentthe epithelium.

In many embodiments, the outer portion comprises a perimeter and whereinthe outer rigidity comprises a rigidity to conform to a boundary of theepithelium inward of the perimeter and to indent the epithelium with atleast a portion of the perimeter.

In many embodiments, the outer portion comprises a perimeter and whereinthe outer rigidity comprises a rigidity to cover at least a portion ofthe perimeter with the epithelium when the covering is adhered to thecornea. The at least the portion of the perimeter may correspond to aninferior portion of the epithelium disposed at an inferior location ofthe cornea. The at least the portion of the perimeter may comprise theinferior portion of the epithelium and a superior portion of theepithelium, and the at least the portion of the epithelium may extendover the perimeter a greater distance on the inferior portion of thecovering than a superior portion of the covering.

In many embodiments, the outer portion comprises a modulus to remodelthe epithelium with an indentation and retain at least a portion of theperimeter of the covering at least partially within the indentation.

In many embodiments, the covering comprises a modulus within a rangefrom about 4 to 20 MPa such that the covering conforms at leastpartially to an ablated stroma when positioned on the cornea andinhibits irregularities. The covering comprising the can inhibit theirregularities in many ways, for example by providing a guide toepithelial growth such that the epithelium grows smoothly, for exampleby sealing the cornea to decrease swelling such as central islands, andfor example, smoothing of the irregularities.

In many embodiments, the covering comprises a modulus within a rangefrom about 4 to 20 MPa such that the covering conforms at leastpartially to an ablated stroma when positioned on the cornea andsmoothes irregularities.

In many embodiments, the covering comprises an inner portion having anamount of rigidity within a range from about 1×10−4 to about 5×10−3(Pa*m̂3) such that the covering conforms at least partially to an ablatedstroma and smoothes epithelium when positioned on the cornea andinhibits irregularities. The range can be from about 2×10−4 to about4×10−3 (Pa*m̂3).

In many embodiments, the covering comprises an inner portion having athickness and a modulus such that a first area the covering about 3 mmacross deflects about 5 um in response a first pressure when the firstpressure is within a first range from about 200 Pa to about 920 Pa, anda second area of the inner portion of the covering deflects about 5 umin response to a second pressure when the second pressure is within asecond range from about 25 Pa to about 120 Pa. The second area maycomprise the first area. The first range can be from about 365 Pa toabout 740 Pa the second range can be from about 45 Pa to about 95 Pa.

In another aspect, embodiments of the present invention provide a methodof treating an eye of a patient, the eye having an epithelium with adefect and an ablated stroma, the method comprising:

providing a covering, wherein the covering contacts the ablated stromaand the epithelium around the defect to define an enclosure to promotegrowth of the epithelium over the ablated stroma.

In another aspect, embodiments of the present invention provide acovering to treat an eye of a patient, the eye having an epithelium witha defect and an ablated stroma, the covering comprising:

an inner portion comprising an inner rigidity to contact the stroma;an outer portion comprising an outer rigidity to define a guide with theinner portion and the ablated stroma to promote growth of the epitheliumalong the guide when the outer portion is adhered to the stroma.

In another aspect, embodiments of the present invention provide acovering to treat an eye of a patient, the eye having an epithelium witha defect and an ablated stroma, the covering comprising:

an inner portion comprising an inner rigidity to contact the stroma tocorrect vision;an outer portion comprising an outer rigidity to define an enclosurewith the inner portion and the ablated stroma to promote growth of theepithelium.

In another aspect, embodiments of the present invention provide acovering to treat an eye of a patient, the eye having an epithelium witha defect, the covering comprising:

an inner portion which covers the defect;an outer portion comprising a perimeter and a modulus to form anindentation in the epithelium when the epithelium regenerates to coverthe defect.

In another aspect, embodiments of the present invention provide a methodof treating an eye of a patient, the eye having an epithelium with adefect, the method comprising: positioning a covering on the cornea tocover the defect, the covering comprising an outer portion comprising aperimeter and a modulus, wherein the covering forms an indentation inthe epithelium when the epithelium regenerates to cover the defect.

In another aspect, embodiments of the present invention provide acovering to treat an eye of a patient, the eye having an epithelium withan irregularity on a ablated stroma, the covering comprises aconformable inner portion to cover the irregularity, and the innerportion comprises an upper surface. The irregularity comprising anirregularity profile, and an outer portion is configured to adhere tothe epithelium. The upper surface profile corresponds to a profile ofthe ablated stroma to correct vision and smooth the irregularity whenthe outer portion adheres to the epithelium.

In many embodiments, the irregularities profile comprises spatialfrequencies and the upper surface profile comprises spatial frequencies,and wherein the inner portion comprises a low pass filter such that theupper surface profile spatial frequencies are lower than the spatialfrequencies of the irregularity profile to correct vision.

In many embodiments, the inner portion comprises a stretchable materialto stretch across the irregularities of the epithelium and smoothirregularities transferred from the irregularity profile in contact withthe lower surface to the upper surface profile when the outer portion isadhered to the epithelium. The inner portion may comprise a stretchablematerial having a thickness profile that smoothes irregularities of theepithelium when the covering is positioned on the cornea. The innerportion may comprises a compressible material to conform to theirregularities of the epithelium with a lower surface and smoothirregularities transferred from the irregularity profile in contact withthe lower surface to the upper surface profile when the outer portion isadhered to the epithelium.

In another aspect, embodiments of the present invention provide a methodtreating an eye of a patient, the eye having an epithelium with anirregularity on a ablated stroma. A covering is provided that comprisesa conformable inner portion to cover the irregularity and an outerportion to adhere to the epithelium. The inner portion comprises anupper surface, and the irregularity comprising an irregularity profile.The inner portion is placed over the ablated stroma, and the outerportion adheres to the epithelium and the inner portion conforms to aprofile of the ablated stroma to correct vision and smooth theirregularity when the outer portion adheres to the epithelium.

In many embodiments, the irregularities profile comprises spatialfrequencies and the upper surface profile comprises spatial frequencies.The inner portion comprises a low pass filter such that the uppersurface profile spatial frequencies are lower than the spatialfrequencies of the irregularity profile to correct vision.

In many embodiments, the inner portion comprises a compressible materialto conform to the irregularities of the epithelium with a lower surfaceand smooth irregularities transferred from the irregularity profile incontact with the lower surface to the upper surface profile when theouter portion is adhered to the epithelium.

In another aspect, embodiments of the present invention provide acovering to treat an eye of a patient, the eye having an epithelium witha defect. The covering comprises an inner portion to cover the defect,and an outer portion comprising an outer rigidity. The outer portioncomprises a superior portion to contact the epithelium superiorly with asuperior rigidity and an inferior portion to contact the epitheliuminferiorly with an inferior rigidity on the patient, in which theinferior rigidity is less than the superior rigidity.

In many embodiments, the superior portion comprises a superior thicknessand the inferior portion comprises an inferior thickness less than thesuperior thickness. The covering may comprise a single piece of materialformed with a mold.

In many embodiments, the superior portion comprises a superior hardnessand the inferior portion comprises an inferior hardness less than thesuperior hardness. The covering may comprise a superior material havinga superior hardness and an inferior material having the inferiorhardness.

In many embodiments, the covering comprises a marking to align thesuperior portion superiorly on the patient and the inferior portioninferiorly on the patient.

In many embodiments, the covering is adhered to an applicator and theapplicator comprises a marking to align the superior portion superiorlyon the patient and the inferior portion inferiorly on the patient.

In another aspect, embodiments of the present invention provide a methodof treating an eye of a patient, the eye having an epithelium with adefect. A covering is provided with an outer portion comprising an outerrigidity, the outer portion comprising a superior portion to contact theepithelium superiorly with a first rigidity and an inferior portion tocontact the epithelium inferiorly with an second rigidity on thepatient, and the first rigidity greater than the second rigidity.

In many embodiments, the inferior portion is aligned with an inferiorportion of the eye and the superior portion is aligned with a superiorportion of the eye when the covering is positioned on the eye.

In another aspect, embodiments of the present invention provide acovering to treat an eye of a patient, the eye having an epithelium anda stroma, the covering comprises a conformable inner portion comprisinga first rigidity to conform to the stroma and guide regeneration of theepithelium, and a conformable outer portion comprising a second rigidityto conform to the epithelium.

In many embodiments, the inner portion comprises a first configurationprior to placement on the cornea and a second configuration when placedon the eye, the second configuration different from the firstconfiguration and conforming substantially to an ablated stromal surfaceof the cornea.

In many embodiments, the second rigidity is less than the firstrigidity.

In many embodiments, the second rigidity is greater than the firstrigidity. The outer portion may comprises an annular rim disposed aroundthe inner portion.

In many embodiments, the first rigidity of the inner portion is greaterthan a rigidity of the epithelium and less than a rigidity of a cornealstroma such that the inner portion smoothes the epithelium when saidinner portion conforms to the stroma.

In many embodiments, the epithelium comprises an epithelial rigidity,and the eye comprises a stroma comprising a stromal rigidity greaterthan the epithelial rigidity. The inner portion comprises a rigiditygreater than the epithelial rigidity and less than the stromal rigiditysuch that the inner portion smoothes the epithelium when the innerportion conforms to the stroma.

In many embodiments, the epithelium comprises an epithelial hardness,and the eye comprises a stroma comprising a stromal hardness greaterthan the epithelial hardness and wherein the inner portion comprises ahardness greater than the epithelial hardness and less than the stromalhardness such that the inner portion smoothes the epithelium andconforms to the stroma.

In many embodiments, the epithelium comprises an epithelial hardness,and the eye comprises a Bowman's membrane comprising a Bowman's membranehardness greater than the epithelial hardness. The inner portioncomprises a hardness greater than the epithelial hardness and less thanthe Bowman's membrane hardness such that the inner portion smoothes theepithelium and conforms to the Bowman's membrane.

In many embodiments, the epithelium comprises an epithelial hardness andwherein the eye comprises a stroma comprising a stromal hardness greaterthan the epithelial hardness and wherein the outer portion comprises ahardness less than the epithelial hardness and less than the stromalhardness such that the outer portion conforms to the epithelium.

In many embodiments, the inner portion comprises silicone and the outerportion comprises silicone. The inner portion may comprise at least oneof a silica or resin filler. For example, the inner portion may comprisethe resin. The at least the inner portion may comprise an opticallyclear material comprising silicone and resin.

In many embodiments, at least the inner portion comprises an opticallyclear material comprising silicone having an index of refraction withina range from about 1.4 to about 1.5.

In many embodiments, the outer portion comprises at least one of silicaor resin filler. For example, the outer portion comprises silicone andresin

In many embodiments, the inner portion comprises a thickness within arange from about 50 um to about 250 um.

In many embodiments, outer portion comprises a thickness within a rangefrom about 10 um to about 60 um.

In many embodiments, a wettable coating is disposed over at least one ofan upper surface or a lower surface of the covering. The wettablecoating may comprise a lubricious coating. The wettable coating maycomprise a contact angle of no more than about 80 degrees. The wettablecoating may comprise a contact angle of no more than about 60 degrees.

In many embodiments, the lower surface may comprise a hydrophobicmaterial, and the lower surface may comprise the inner portion and theouter portion.

In many embodiments, the at least the outer portion comprises a lowersurface composed of a sticky, tacky, hydrophobic material.

In many embodiments, the inner portion comprises the lower surfacecomposed of the sticky, tacky, hydrophobic material.

In many embodiments, an upper surface comprises wettable coatingextending over at least the inner portion. The wettable coatingcomprises polyethylene glycol (PEG). The PEG coating can be disposed ona Parylene™ coating.

In many embodiments, the wettable coating comprises a plasma coating.The plasma coating may comprise a luminous chemical vapor deposition(LCVD) film. The plasma coating may comprise at least one of ahydrocarbon, for example CH4, O2 or fluorine containing hydrocarbon, forexample CF4

In many embodiments, plasma coating comprises a polyethylene glycol(PEG) coating.

In many embodiments, wettable coating comprises2-hydroxyethylmethacrylate (HEMA). The HEMA can be disposed on aParylene™ coating.

In many embodiments, the wettable coating comprises N-vinylpyrrolidone(NVP). The NVP can be disposed on a Parylene™ coating.

In many embodiments, inner portion is affixed to outer portion. Theinner portion may comprise a first silicone and the outer portion maycomprise a second silicone, and the first silicone of the inner portioncan be affixed to the second silicone of the outer portion.

In many embodiments, the covering comprises a single piece.

In many embodiments, the covering comprises a single piece of materialformed in a mold.

In many embodiments, an intermediate portion is disposed between theinner portion and the outer portion, the intermediate portion comprisinga taper extending from inner portion to outer portion. The taper maycomprise a radial width within a range from about 0.5 mm to about 2.0 mm

In many embodiments, the outer portion comprises an annular flangeextending circumferentially around the inner portion and wherein theouter portion extends radially comprises a radial width within a rangefrom about 0.05 mm to about 1.2 mm

In many embodiments, the inner portion comprises a distance acrosswithin a range from about 3 to about 8 mm.

In many embodiments, the outer portion comprises a distance acrosswithin a range from about 6 to about 12 mm.

In many embodiments, the covering comprises a lower surface disposed ona lower side to contact the eye extending along the inner portion andthe outer portion and wherein the lower surface comprises at least oneof a spherical surface, a bi-curve surface or an aspheric surface.

In many embodiments, the inner portion of the covering comprises anoptical power of no more than about +/−1 D to correct vision of thepatient when the inner portion conforms to the ablated surface andsmoothes the epithelium.

In another aspect, embodiments of the present invention provide acovering to treat an eye of a patient, the eye having an epithelium. Thecovering comprises an inner portion comprising an inner first rigidityto smooth the epithelium. An outer portion comprises an outer secondrigidity. A conformable intermediate portion is disposed between theinner portion and the outer portion. The conformable intermediateportion comprises a third rigidity to conform to the epithelium, and thethird rigidity is less than the first rigidity and the second rigidity.

In many embodiments, the outer second rigidity is greater than the innerfirst rigidity.

In many embodiments, the outer second rigidity is no more than the innerfirst rigidity.

In many embodiments, the inner portion comprises a first material tosmooth the epithelium and the intermediate portion comprises a softmaterial to conform to the epithelium. The outer portion may comprisethe soft material. The outer portion may comprise the first material.The first material may comprise a rigid material having a Shore Adurometer hardness parameter of at least about 60, and the secondmaterial may comprise a soft material having Shore A durometer hardnessparameter of no more than about 70.

In many embodiments, the first material comprises a first siliconecomprising a first hardness and the soft material comprises a secondsilicone having a second hardness less than the first hardness.

In many embodiments, the inner portion comprises an inner firstthickness, the outer portion comprising an outer second thickness, themiddle portion comprising a third thickness, and the third thickness isless than the inner first thickness and the outer second thickness.

In many embodiments, the inner portion comprises a first material tosmooth the epithelium and the intermediate portion comprises the firstmaterial to conform to the epithelium.

In many embodiments, the covering comprises a single piece of materialformed from a mold.

In another aspect, embodiments of the present invention provide acovering to treat an eye of a patient, the eye having an epithelium. Thecovering comprises an inner portion comprising an optical surface. Anouter portion comprises an outer perimeter, and the outer perimetercomprises a chamfer to contact the epithelium to seal the cornea.

In another aspect, embodiments of the present invention provide a methodof treating an eye of a patient, the eye having an epithelium and astroma. A covering is placed over the eye. The covering comprises aconformable inner portion comprising a first rigidity and a conformableouter portion comprising a second rigidity, and the conformable innerportion conforms to the stroma and smoothes the epithelium and the outerportion conforms to the epithelium.

In another aspect, embodiments of the present invention provide a methodof treating an eye of a patient, the eye having an epithelium and anablated stromal surface. A covering is placed over the eye, and thecovering comprise a conformable inner portion comprising a firstrigidity and a conformable outer portion comprising a second rigidity.The conformable inner portion conforms to the ablated surface andsmoothes the epithelium, and the outer portion comprising the secondrigidity conforms to the epithelium.

In many embodiments, the inner portion of the covering comprises anoptical power of no more than about +/−1 D to correct vision of thepatient when the inner portion conforms to the ablated surface andsmooth the epithelium.

In many embodiments, the inner portion of the covering comprises asubstantially uniform thickness to correct vision of the patient whenthe inner portion conforms to the ablated surface and smooth theepithelium.

In many embodiments, the inner portion comprises a first configurationprior to placement on the cornea and a second configuration when placedon the eye, the second configuration different from the firstconfiguration.

In another aspect, embodiments of the present invention provide a methodof manufacturing a therapeutic covering. An inner component ispositioned in a mold. A flowable material is injected into the mold tocontact the inner component along at least a periphery of the innercomponent. The flowable material is cured to form the covering. Thecovering is removed from the mold.

In many embodiments, the first component comprises an opticallytransparent material.

In many embodiments, the first component comprises an opticallytransparent material comprising silicone and resin.

In many embodiments, the flowable material comprises silicone.

In many embodiments, the flowable material comprises resin.

In many embodiments, at least an upper side of the covering is coatedwith a wettable material.

In many embodiments, the covering is placed in a container. The coveringcan be dried prior to placement in the container. The covering can besealed in the container in a substantially dry configuration.

In many embodiments, the covering is connected to an applicator andplaced in the container in a substantially dry configuration.

In many embodiments, a solvent is evaporated to adhere the covering tothe applicator. The solvent may comprises an alcohol, for example.

In another aspect, embodiments of the present invention provide a methodof placing a covering on a cornea of an eye having an epithelium with adefect. A dry covering is provided, the covering having a configurationfor placement on the eye. The cornea is dried to remove at least someliquid from the cornea. The dry covering is advanced in theconfiguration toward the eye to contact the epithelium and cover thedefect with the dry covering.

In many embodiments, the dry covering is advanced with an applicatoradhered to the covering in an expanded configuration.

In many embodiments, covering comprises an outer portion having a lowersurface that sticks to the epithelium of the dry eye.

In many embodiments, the lower surface of the outer portion comprises ahydrophobic sticky tacky surface.

In many embodiments, the eye is exposed to a gas to dry the eye.

In many embodiments, the epithelial defect comprises a debridement.

In many embodiments, the epithelial defect comprises a debridement andwherein the eye comprises an ablated stroma within the debridement. Thecovering can contact the ablated stroma and the epithelium without aliquid disposed between the covering and the epithelium.

In many embodiments, a liquid is not disposed between the covering andepithelium when the covering contacts the epithelium.

In many embodiments, the covering is positioned substantially uniformlyon the dried eye.

In many embodiments, the covering is positioned substantially uniformlyon the dried eye with an applicator.

In another aspect, embodiments of the present invention provide anapplicator to position a covering on an eye. The applicator comprises asupport having a surface to contact at least a peripheral portion of thecovering to stick to the covering.

In many embodiments, the surface comprises a curved surface. The curvedsurface may stick to the covering when the curved surface and the atleast the peripheral portion each comprise a dry surface without aliquid disposed therebetween. The curved surface may comprise a stickytacky surface when dry to hold the covering and a slippery surface whenwet to release the covering. The curved surface can be configured toadhere to the covering with block adhesion and release the covering inresponse to peeling of the covering from the curved surface.

In many embodiments, the curved surface comprises silicone.

In many embodiments, the curved surface comprises a wettable coating.

In many embodiments, the support comprises an annular ring having thecurved lower surface disposed on a lower side of the ring and inclinedto contact the peripheral portion of the covering.

In many embodiments, the support defines an opening sized for a surgeonto view at least a pupil of the eye when the covering is positioned onthe eye.

In many embodiments, a handle is affixed to the support for placement onthe covering when the handle is grasped by a surgeon.

In many embodiments, the support comprises foam coupled to the coveringto position the covering on the eye and to release the covering when thecovering is positioned on the eye.

In another aspect, embodiments of the present invention provide anapplicator to position a covering on an eye. The applicator comprises asupport having a curved surface to contact at least a peripheral portionof the covering. The curved surfaces adheres to the covering when dryand releases the covering when wet.

In another aspect, embodiments of the present invention provide anapplicator to position a covering on an eye of a patient. The applicatorcomprises a support comprising a rigid first component and a secondcomponent movable relative to the rigid first component to position thecovering on the eye, and the movable component comprises at least aportion viewable therethrough.

In many embodiments, the at least the portion is viewable therethroughfrom the eye on a first side of the support to an object on a secondside of the support opposite the first side when the support and thecovering are positioned in front of the eye to place the covering on theeye.

In many embodiments, the at least the portion is viewable therethroughfrom an operating microscope positioned on the second side of thesupport to a tissue structure of the eye disposed on the first side whenthe support and the covering are positioned in front of the eye to placethe covering on the eye.

In many embodiments, the rigid component comprises a window. The windowof the rigid component may comprise an opening defined with the rigidcomponent and sized to receive the movable component. The at least theportion comprises a window disposed within the window of the support.

In many embodiments, the at least the portion comprises a windowcomposed of a transparent material.

In many embodiments, the at least the portion comprises an inner openingdefined with an outer portion of the movable second component.

In many embodiments, the support comprises a first configuration tocarry the covering and a second configuration to release the covering.The movable component can urge the covering toward the eye when thesupport transitions from the first configuration to the secondconfiguration. The movable component peels the covering from the supportwhen the support transitions from the first configuration to the secondconfiguration.

In many embodiments, the movable component comprises a thin transparentflexible sheet coupled to the rigid component to urge the coveringtoward the eye.

In many embodiments, the rigid component and the movable componentdefine a chamber to urge the covering onto the eye when fluid is passedinto the chamber.

In many embodiments, the movable component comprises a popper.

In many embodiments, the movable component comprises an opticallytransparent material sized to fit within the rigid component to urge thecovering toward the eye. The rigid first component may comprise anannulus having an inner diameter, and the movable second component maycomprise a disc having a diameter sized to fit within the innerdiameter. The movable component can be coupled to the shield to urge theshield toward the eye.

In many embodiments, support comprises a single piece of material formedfrom a mold, the rigid component comprising the material and the movablecomponent comprising the material wherein the rigid component comprisesa thickness greater than the movable component such that a shape of therigid component is retained substantially when the movable componentflexes.

In another aspect, embodiments of the present invention provide aapplicator to position a covering on an eye of a patient. The applicatorcomprises a rigid first component to carry the covering with an outerportion of the covering and position the covering on the eye. A secondcomponent is movable relative to the rigid first component to contact aninner portion of the covering and separate the covering from the firstrigid component when the covering is positioned on the eye. The movablecomponent may comprise at least a portion viewable therethrough.

In many embodiments, the rigid first component comprises an openingsized to receive second component.

In many embodiments, the rigid first component comprises an openingsized to receive second component.

In many embodiments, the rigid first component comprises a lowerinclined surface to stick to the covering at the outer portion, and thesecond component comprises a lower surface to contact the inner portionof the covering and peel the covering from the lower inclined surfacewhen the second component moves toward the eye.

In many embodiments, a handle is connected to the rigid first componentand a structure extending between the handle and the movable componentto urge the movable component toward the eye when the handle is graspedby a user.

In another aspect, embodiments of the present invention provide anapplicator to position a covering on a cornea of an eye of a patient.The applicator comprises a handle, and a first component to carry thecovering and position the covering on the cornea of the eye. A rigidsecond component is rigidly coupled to the handle and the firstcomponent to fix the eye when the covering is positioned on the eye withthe first component.

In many embodiments, the first component comprises a first annularportion to couple to the covering and position the covering on the eye,and the second component comprises a fixation ring to fix the eye.

In another aspect, embodiments of the present invention provide anapplicator to position a covering on a cornea of an eye of a patient.The applicator comprises a handle, and a first component to carry thecovering and position the covering on the cornea of the eye. Theapplicator comprises a second component to de-enervate the eye with atleast one of a substance or cooling when the covering positioned on thecornea with the handle.

In another aspect, embodiments of the present invention provide anapplicator to position a covering on a cornea of on an eye of a patient.The apparatus comprises a handle to position the covering on the eye. Atleast two contact pads to contact the covering are coupled to thehandle, in which each pad comprises a lower surface to couple to thecovering, and the at least two pads are separated by a distance. Theapparatus comprises at least two extensions, in which each extension iscoupled to one of the pads and extends between said pad and the handle,and the at least two extensions are inclined relative to the pads andseparated such that the patient can view an object when the covering isplaced on the eye with the pads separated by the distance.

In many embodiments, the lower surface of each pad comprises an inclinedsurface, and the extensions are configured to separate to release thecovering when the covering is positioned on the cornea.

In many embodiments, the inclined lower surface of each pad isconfigured to adhere to the covering with block adhesion to carry thecovering prior to placement and wherein the extensions are configured toseparate the pads along a path to peel the covering away from thecovering away from the pads when the pads separate to release thecovering.

In many embodiments, each contact pad comprises a roller configured toroll outward along the covering when the pad is pressed toward the eyewith the handle.

In many embodiments, each contact pad comprises a concave rollerrotationally coupled to said extension to roll outward along thecovering when the pad is pressed toward the eye with the handle and theextension.

In another aspect, embodiments of the present invention provide anapparatus to cover an eye. The apparatus comprises a dry covering havingan upper surface. A support having a lower surface is coupled to theupper surface to position the covering on the eye and release thecovering when the covering is positioned on the eye.

In many embodiments, the lower surface is coupled to an outer portion ofthe covering to release the covering.

In many embodiments, the lower surface is coupled to an outer portion ofthe covering with block adhesion to release the covering in response topeeling of the covering from the support.

In many embodiments, the lower surface comprises a non-wettable surfacein contact with the dry covering.

In many embodiments, the lower surface comprises a wettable surfacecoating in contact with the dry covering.

In many embodiments, the dry covering comprises a non-wettable surfacein contact with the lower surface.

In many embodiments, the dry covering comprises a wettable surface incontact with the lower surface.

In many embodiments, the lower surface comprises a wettable coating.

In many embodiments, the lower surface extends along a curve to definean opening, and the lower surface comprises an inclined angle along thecurve hold the covering for placement on the eye. The dry covering canbe adhered to the lower surface and wherein the lower surface releasesthe covering when wet. The support comprises silicone and the coveringcomprises silicone. The silicone of the support can contact the siliconeof the covering to adhere the covering to the support.

In many embodiments, the covering comprises an upper surface comprisinga wettable coating disposed thereon, and the wettable coating of thecovering sticks to the lower surface of the support. The wettablecoating on the upper surface of the covering can separates from thelower curved surface when wet. The lower surface may comprise ahydrophobic material in contact with the wettable coating on the uppersurface of the covering to release the lower curved surface when wet.

In many embodiments, the lower surface comprises a wettable material incontact with the wettable coating on the upper surface of the coveringto adhere the lower curved surface to the upper surface when dry and torelease the upper surface when wet.

In many embodiments, the dry covering comprises an optically transparentsurface having an optical power of no more than about +/−1 D.

In another aspect, embodiments of the present invention provide anmethod of placing a covering on a cornea of an eye having an epitheliumwith a defect. A fixation light is provided to a patient to view withthe eye. The covering is positioned over the eye of the patient andseparated from the cornea of the eye, and the patient views the fixationlight when the covering is positioned over the eye and separated fromthe cornea. The covering is advanced toward the eye to contact and coverthe defect when the patient views the fixation light.

In many embodiments, the patient fixates on the fixation light tostabilize the eye when the covering is advanced toward the eye. Asurgeon can view the eye through an operating microscope to align thecovering with the eye when the covering is advanced toward the eye.

In many embodiments, the covering comprises at least a portion viewabletherethrough and wherein the patient fixates on the fixation light withlight from the fixation light transmitted through the at least theportion when the covering is advanced toward the eye. The covering maycomprise a dry optically transparent covering having an optical power ofno more than about +/−1 D when positioned in front of the eye. The atleast the portion may comprise a dry anterior surface without a liquiddisposed thereon and a dry posterior surface without a liquid disposedthereon and wherein the patient views the fixation target through thedry anterior surface and the dry posterior surface.

In many embodiments, the surgeon views a structure of the eye throughthe at least the portion to align the covering with the eye when thecovering is advanced toward the eye. The structure of the eye maycomprise at least one of the epithelial defect, an iris of the eye, apupil or a limbus of the eye.

In many embodiments, the covering is advanced toward the eye with anapplicator coupled to the covering. The applicator may comprise awindow, and the patient can views the fixation light through the windowwhen the applicator is advanced toward the eye. The covering can bereleased from the applicator when the covering is positioned in contactwith the cornea.

In many embodiments, the applicator holds the covering in asubstantially expanded configuration for placement on the cornea whenthe covering is advanced toward the eye.

In another aspect, embodiments of the present invention provide a methodof removing a covering from an eye. A covering is provided positionedover a regenerated epithelium of the eye. An elongate structure ispositioned having a lumen disposed therein, and the lumen extends to anopening on the distal end and the opening is positioned under thecovering. A liquid is injected through the opening positioned under thecovering so as to separate the covering from the regenerated epitheliumalong a lower surface of the covering.

In many embodiments, the opening comprises a cross sectional size havinga maximum distance across extending a first direction and wherein thefirst direction is aligned substantially with a lower surface of thecovering to inject the liquid along the lower surface of the covering toseparate the covering from the regenerated epithelium.

In another aspect, embodiments of the present invention provide a methodof removing a covering from an eye having an epithelium and ablatedstroma. the covering is provided positioned over a regeneratedepithelium substantially covering the ablated stroma. An elongatestructure is positioned having a lumen disposed therein. The lumenextends to an opening on the distal end. A liquid is injected to deliverthe liquid to a distal end through the opening and under the covering toseparate the covering from the regenerated epithelium along a lowersurface of the covering.

In another aspect, embodiments of the present invention provide anapparatus to remove covering from an eye. The apparatus comprises anelongate structure having a proximate portion and a distal portion. Theelongate structure has a lumen disposed therein to deliver a liquid to adistal end of the distal portion. The lumen extends to an opening on thedistal end, and the opening has a sectional size with a first longerdimension across extending in a first direction and a second smallerdistance across extending in a second direction. An elongate supportextends in an elongate direction, and the elongate support is attachedto the proximal portion of the elongate structure and graspable by auser to position the distal end under the covering to align the maximumdistance across a lower surface of the covering when the handle ispositioned near a temple of the patient.

In another aspect, embodiments of the present invention provide anapparatus to remove a covering from an eye. The apparatus comprises anelongate structure having a lumen disposed therein to deliver a liquidto a distal end, wherein the lumen extends to an opening on the distalend. The opening has a cross sectional size with a first longerdimension across extending in a first direction and a smaller dimensionacross extending in a second direction. An elongate support extends inan elongate direction, the elongate support graspable by a user toposition the distal end under a temporally disposed portion of aperimeter of the covering when the handle is positioned near a temple ofthe patient. The elongate structure comprises a bend between the supportand the distal end and wherein the maximum distance across is alignedwith the temporally disposed portion of the perimeter of the coveringwhen the handle is positioned near the temple.

In another aspect, embodiments of the present invention provide a methodof treating an eye of a patient following PRK surgery, the eye having anepithelium with a defect and an ablated stroma. A covering is placedover the ablated stroma to cover the epithelial defect and couple to thecornea so as to improve to at least about 20/40 between 24 hours to 72hours post-op and wherein the patient without the placed covering wouldhave vision of less than about 20/40 between 24 to 72 hours post-op.

In many embodiments, the vision is improved to at least about 20/30between 24 hours to 72 hours post-op and wherein the patient without theplaced covering would have vision of less than about 20/30 between 24 to72 hours post-op.

In many embodiments, the vision is improved to at least about 20/25between 24 to 72 hours post-op and wherein the patient without theplaced covering would have vision of less than about 20/25 between 24 to72 hours post-op.

In many embodiments, the vision is improved to at least about 20/20between 24 hours to 72 hours post-op and wherein the patient without theplaced covering would have vision of less than about 20/30 between 24 to72 hours post-op.

In another aspect, embodiments of the present invention provide a methodof treating an eye of any of a population of patients following PRKsurgery, the population of PRK patients having at least about 40% ofpatients seeing 20/40 or better between 24 to 72 hours post-op. The eyehas an epithelium with a defect and a successfully ablated stroma. Acovering is placed over the ablated stroma to cover the epithelialdefect and improve vision such that the patient is a member of thepopulation.

In many embodiments, the population of patients has at least about 60%of patients seeing 20/40 or better between 24 to 72 hours post-op.

In many embodiments, the population of patients has at least about 80%of patients seeing 20/40 or better between 24 to 72 hours post-op.

In many embodiments, the population of patients has at least about 90%of patients seeing 20/40 or better between 24 to 72 hours post-op.

In another aspect, embodiments of the present invention provide acovering to treat an eye of a patient following PRK surgery, the eyehaving an epithelium with a defect and an ablated stroma. The coveringcomprises a curved body to couple to the cornea and cover the ablatedstroma and the epithelial defect so as to improve vision to at leastabout 20/40 between 24 to 72 hours post-op, and the eye without thecovering would have vision of less than 20/40 between 24 to 72 hourspost-op.

In many embodiments, the vision is improved to at least about 20/30between 24 hours to 72 hours post-op and wherein the patient without theplaced covering would have vision of less than about 20/30 between 24 to72 hours post-op.

In many embodiments, the vision is improved to at least about 20/25between 24 to 72 hours post-op and wherein the patient without theplaced covering would have vision of less than about 20/25 between 24 to72 hours post-op.

In many embodiments, the vision is improved to at least about 20/20between 24 hours to 72 hours post-op and wherein the patient without theplaced covering would have vision of less than about 20/30 between 24 to72 hours post-op.

In another aspect, embodiments of the present invention provide acovering to treat an eye of a patient following PRK surgery, the PRKsurgery comprising epithelial removal from a region of the cornea of theeye and ablation of stroma of the cornea underlying the region such thatthe eye, with an appropriate standard contact lens disposed on thecornea and without the treatment, would have visual acuity of worse than20/40 throughout the period between 24 to 72 hours after the PRKsurgery. The covering comprises a curved body with a concave surfacereceiving the cornea so as to cover the ablated stroma and a convexsurface over which an eyelid passes without dislodging the curved bodyfrom the cornea during blinking of the eye. The curved body istransparent and engagement of the curved body against the corneamitigating the epithelial removal so as to improve the visual acuity ofthe eye therethrough to at least about 20/40 between 24 to 72 hoursafter the PRK surgery.

In many embodiments, the vision is improved to at least about 20/30between 24 hours to 72 hours post-op and wherein the patient without theplaced covering would have vision of less than about 20/30 between 24 to72 hours post-op.

In many embodiments, the vision is improved to at least about 20/25between 24 to 72 hours post-op and wherein the patient without theplaced covering would have vision of less than about 20/25 between 24 to72 hours post-op.

In many embodiments, the vision is improved to at least about 20/20between 24 hours to 72 hours post-op and wherein the patient without theplaced covering would have vision of less than about 20/30 between 24 to72 hours post-op.

In another aspect, embodiments of the present invention provide acovering to treat an eye of any of a population of patients followingPRK surgery, the population having at least about 40% of patients seeing20/40 or better between 24 to 72 hours post-op, the eye having anepithelium with a defect and a successfully ablated stroma. The coveringcomprises a curved body to couple to the cornea and cover the ablatedstroma and epithelial defect such that the patient is a member of thepopulation.

In another aspect, embodiments of the present invention provide acovering to treat an eye of a patient following PRK surgery, the patientincluded within a population of PRK patients receiving PRK surgery, eachPRK surgery comprising epithelial removal from a region of the cornea ofthe associated eye and ablation of stroma of the cornea underlying theregion, the epithelial removal degrading short-term visual acuities ofthe eyes after the PRK. The covering comprises a curved body with aconcave surface receiving the cornea so as to cover the ablated stromaand a convex surface over which an eyelid passes without dislodging thecurved body from the cornea during blinking of the eye, the curved bodybeing transparent and mitigating the short-term visual acuitydegradation when disposed on the eye. The mitigation is sufficient that40% of the eyes of the patients of the population would have visualacuities of at least about 20/40 between 24 to 72 hours after the PRKsurgery.

In many embodiments, the population of patients has at least about 60%of patients seeing 20/40 or better between 24 to 72 hours post-op.

In many embodiments, the population of patients has at least about 80%of patients seeing 20/40 or better between 24 to 72 hours post-op.

In many embodiments, the population of patients has at least about 90%of patients seeing 20/40 or better between 24 to 72 hours post-op.

In another aspect, embodiments of the present invention provide acovering to treat an eye of a patient. The covering comprises a curvedbody to fit they eye. The body has a modulus within a range from about 4MPa (Mega Pascal's) to about 20 MPa.

In many embodiments, the body comprises an elastomer. The elastomer maycomprise silicone polymer formed with one or more of vinylpolymerization, peroxide polymerization or hydrosilation.

In many embodiments, the body comprises contact lens having a centrallens portion having a center stiffness of at least about 2 psi*mm2coupled to an outer lenticular junction portion having a lenticularjunction stiffness of at least about 5 psi*mm2.

In many embodiments, the body comprises an amount of water within arange from about 0 to 35% and wherein the body comprises a Dk of 100 ormore. The body may comprise silicone comprising one or more of siliconeelastomer or silicone hydrogel. The range of water can be from about 0to 10% and the Dk is 100 or more. The body may comprise the siliconeelastomer and the range of water is from about 0 to 5% and the Dk is 100or more.

In many embodiments, the body comprises the silicone hydrogel and thesilicone hydrogel comprises a low ion permeability and the range ofwater is from about 5% to about 35% and the Dk is 100 or more. The lowion permeability may comprise an Ionoton Ion Permeability Coefficient ofno more than about 0.25×10−3 cm2/sec. The low ion permeability maycomprise an Ionoton Ion Permeability Coefficient of no more than about0.08×10−3 cm2/sec. The low ion permeability may comprise an Ionoton IonPermeability Coefficient of no more than about 2.6×10−6 mm2/min. The lowion permeability may comprise an Ionoton Ion Permeability Coefficient ofno more than about 1.5×10−6 mm2/min.

In many embodiments, the body comprises a wettable surface having a tearbreak up time of no less than about five seconds when placed on the eye.The wettable surface may comprise a coating of one or more of luminouschemical vapor deposition (LCVD), hydrogel, 2-hydroxyethylmethacrylate(HEMA), methacrylic acid (MA), methyl methacrylate (MMA),N,N-dimethylacrylamide (DMA); N-vinyl pyrrolidone (NVP),phosphorylcholine (PC), poly vinyl alcohol (PVA) or polyvinylpyrrolidone (PVP), tris-(trimethylsiloxysilyl) propylvinyl carbamate(TPVC); N-carboxyvinyl ester (NCVE); silicone hydrogel,poly[dimethylsiloxyl] di [silylbutanol] bis[vinyl carbamate] (PBVC);silicate, plasma treated silicone hydrogel, plasma coating producingglassy islands, 25 nm plasma coating with high refractive index.

In many embodiments, wettable surface comprises the material of thebody. The material of the body and surface may comprise hydrogel. Thematerial of the body comprises an optically clear silicone elastomercomprising silicate, and the silicone elastomer may comprise silicatetreated with plasma to generate the wettable surface.

In many embodiments, the wettable surface comprises hydrogel and thebody comprises silicone elastomer and wherein the hydrogel is disposedsilicone elastomer.

In many embodiments, the body comprises an inner portion and an outerportion, wherein the inner portion comprises a lower surface having afirst radius of curvature to fit an ablated region of a cornea of theeye and the outer portion comprises a lower surface having a secondradius of curvature to fit an unablated region of the cornea of the eye.

In many embodiments, the body comprises a lower surface having an oblateshape to fit an ablated region of a cornea of the eye and to fit anunablated region of the cornea.

In many embodiments, the body comprises a first curved portion, a secondcurved portion, and a third curved portion, wherein the first curvedcomprises a first lower surface having a first radius of curvature tofit an ablated region of a cornea the eye, the second curved portioncomprising a second lower surface having a second radius of curvature tofit an unablated region of the cornea of the eye, the third curvedportion comprising a third lower surface having a third radius ofcurvature to fit a sclera of the eye.

In many embodiments, the second radius of curvature to fit the unablatedcornea is less than the third radius of curvature to fit the sclera.

In many embodiments, the curved body comprises an inner portion to sealthe cornea and an outer portion having fenestrations extending through athickness of the body to pass a medicament to treat pain when the lensis adhered to the cornea.

In another aspect, embodiments provide a method of treating an eye aneye of a patient. A covering comprising a curved body is placed on thecornea of the eye. The body has a modulus within a range from about 4MPa (Mega Pascal's) to about 20 MPa.

In many embodiments, the eye comprises an epithelium and an ablatedstroma and wherein covering adheres to the epithelium and conforms atleast partially to the ablated stroma to improve the vision of thepatient. The covering may inhibit irregularities of one or more of theepithelium or the ablated stroma when the covering conforms at leastpartially to the ablated stroma. For example, the covering may smoothirregularities of the cornea.

In another aspect, embodiments provide a covering to treat an eye of apatient. The covering comprises a curved body to fit the eye. The bodycomprises an inner portion and an outer portion. The inner portion hasan amount of rigidity within a range from about 1×10E-4 to about 5×10E-4Pa*m̂3 (Pascal*meters cubed), the outer portion has an amount of rigidityless than the inner portion. The range can be from about 2×10E-4 toabout 4×10E-4 Pa*m̂3 (Pascal*meters cubed).

In many embodiments, the inner portion comprises a first layer of afirst material and a second layer of a second material, the firstmaterial comprising a soft material having a modulus within a range fromabout 0.1 to about 5 MPa, the second material having a modulus within arange from about 5 to about 1900 MPa.

In many embodiments, the inner portion comprises a third layer of athird material having a third modulus within a range from about 0.1 toabout 5 MPa.

In many embodiments, the first material comprises a first silicone andthe second material and the third material comprise a second silicone,the first silicone comprising a first modulus within a first range fromabout 5 to 35 MPa, the second silicone comprising a modulus from about0.1 to 5 MPa.

In many embodiments, the inner portion comprises an RGP material and theouter portion and the third portion comprise a hydrogel.

In many embodiments, the inner portion comprises a first curved portionand the outer portion comprises a second curved portion and a thirdcurved portion. The first curved portion comprises a first lower surfacehaving a first radius of curvature to fit an ablated region of a corneathe eye. The second curved portion comprises a second lower surfacehaving a second radius of curvature to fit an unablated region of thecornea of the eye. The third curved portion comprises a third lowersurface having a third radius of curvature to fit a sclera of the eye.

In many embodiments, the first radius of curvature comprises an apicalradius of curvature and the second radius of curvature corresponds to aconic constant.

In many embodiments, the third radius of curvature comprises no morethan about 10 mm and a modulus of no more than about 5 MPa and athickness of no more than about 200 um so as to stretch substantiallyand resist movement of the inner portion when placed on the sclera.

In many embodiments, the third radius of curvature comprises no morethan about 9 mm and an amount of rigidity of no more than about 4E-5Pa*m̂3 so as to stretch substantially for comfort and resist movement ofthe inner portion when placed on the sclera.

In many embodiments, the third curved portion comprises a maximumdimension across within a range from about 12 to 16 mm to contact theconjunctiva and couple to the sclera of the eye.

In many embodiments, the range is from about 14 to 16 mm to resistmovement of the inner portion when the third curved portion is placed onthe conjunctiva and coupled to the sclera.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an eye suitable for incorporation of the covering asdescribed herein, in accordance with embodiments of the presentinvention;

FIG. 1-1A shows an ablated eye immediately following refractive surgeryresulting in an epithelial defect, suitable for incorporation inaccordance with embodiments of the present invention:

FIG. 1-1B shows an ablated eye about 1 day following refractive surgeryresulting in an epithelial defect, suitable for incorporation inaccordance with embodiments of the present invention:

FIG. 1-1C shows an ablated eye when the epithelium has regeneratedfollowing refractive surgery resulting in an increased epithelialthickness centrally at about 3 days, suitable for incorporation inaccordance with embodiments of the present invention:

FIG. 1-2A shows a covering positioned on an eye having an epithelialdefect, in which the covering abuts the cornea to seal the cornea, inaccordance with embodiments of the present invention:

FIG. 1-2B shows a smooth layer of regenerated epithelium substantiallycover an ablated profile, in accordance with embodiments of the presentinvention;

FIG. 1A shows a covering positioned on an eye having an epithelialdefect, in which an outer portion of the covering abuts and conforms atleast partially to the cornea to seal the cornea, in accordance withembodiments of the present invention:

FIG. 1A1 shows a covering positioned on an eye and blinking of the eye,in accordance with embodiments of the present invention:

FIG. 1B1 shows a covering sized to seal a cornea, in accordance withembodiments of the present invention:

FIG. 1B2 shows the covering conforming to ablated stromal tissue andguiding regeneration of the epithelium over the ablated stroma, so as topromote vision, in accordance with embodiments of the present invention;

FIG. 1B2A shows a covering forming an indentation in the epithelium suchthat the epithelium extends over at least a portion of the perimeter ofthe covering, in accordance with embodiments of the present invention;

FIG. 1B2B shows a covering forming an indentation in the epithelium, inaccordance with embodiments of the present invention:

FIG. 1B2C shows a covering abutting the cornea to seal the corneawithout forming a substantial indentation in the epithelium, inaccordance with embodiments of the present invention:

FIG. 1C shows a covering comprising a single piece of material having aninner thickness greater than an outer thickness, in accordance withembodiments of the present invention;

FIG. 1C1 shows a covering as in FIGS. 1-2A to 1B2 having an innerportion comprising an inner thickness and an inner material and an outerportion comprising an outer thickness and an outer material, in whichthe inner thickness is greater than the outer thickness, in accordancewith embodiments of the present invention;

FIG. 1C1A shows a covering as in FIG. 1C1 adhered to the cornea with asmooth upper surface and a lower surface conforming to irregularity ofthe cornea comprising a central island of the stroma, in accordance withembodiments of the present invention;

FIG. 1C2 shows a covering as in FIGS. 1-2A to 1B2 having an innerportion comprising an inner thickness and an inner material and an outerportion comprising an outer thickness and an outer material, in whichthe inner thickness is greater than the outer thickness and the outermaterial extends around the inner material, in accordance withembodiments of the present invention;

FIG. 1C2A shows a covering as in FIG. 1C1 adhered to the cornea with asmooth upper surface and a lower surface conforming to irregularity ofthe cornea near the edge of the ablation, in accordance with embodimentsof the present invention;

FIG. 1D shows a covering as in FIGS. 1-2A to 1B2 having an inner portioncomprising an inner thickness and an inner material and an outer portioncomprising an outer thickness and an outer material, in which the innerthickness is substantially similar to the outer thickness, in accordancewith embodiments of the present invention;

FIGS. 1E and 1F show top and side views, respectively, of a coveringcomprising an inner portion and an outer portion, as in FIGS. 1A to 1B2and a peripheral rim portion disposed around the outer portion, inaccordance with embodiments of the present invention;

FIG. 1G shows a covering comprising an inner portion and an outerportion comprising a taper, in accordance with embodiments of thepresent invention;

FIG. 1G1 shows a covering comprising an inner portion and an outerportion comprising a taper and an outer rim of substantially uniformthickness peripheral to the taper, in accordance with embodiments of thepresent invention;

FIGS. 1G1A to 1G1G show a covering as in FIG. 1G1 and dimensionssuitable for use with experiments, clinical studies and patienttreatment in accordance with embodiments;

FIG. 1H1 shows spatial frequency and elevation smoothing of anepithelial irregularity transferred to a front surface of a covering asin FIG. 1-2A, in accordance with embodiments.

FIG. 1H2 shows spatial frequency and elevation smoothing of theepithelial irregularity with a plot of height relative to a referencesphere for the upper surface of the covering and the upper surface ofthe irregularity;

FIG. 1I1 shows inhibition of transfer of an epithelial irregularity to afront surface of a covering, in accordance with embodiments.

FIG. 1I2 shows elevation smoothing of the epithelial irregularity with aplot of height relative to a reference sphere for the upper surface ofthe covering and the upper surface of the irregularity;

FIG. 1I3 shows a thickness profile of the covering as in FIG. 1I2 so asto smooth the front surface of the covering, in accordance withembodiments of the present invention;

FIG. 1J1 shows a covering having a bicurve profile to fit an ablatedcornea, in accordance with embodiments of the present invention;

FIG. 1J2 shows a covering having an oblate profile to fit an ablatedcornea, in accordance with embodiments of the present invention;

FIG. 1J3 shows a covering having a tricurve profile to fit sclera and anablated cornea, in accordance with embodiments of the present invention;

FIG. 1J4 shows a covering having a curved profile to fit sclera and anoblate profile to fit ablated cornea, in accordance with embodiments ofthe present invention;

FIG. 1J5 shows a covering having a tricurve profile to fit sclera and anablated cornea similar to FIG. 1J3, in accordance with embodiments ofthe present invention;

FIG. 1J6 shows a tapered edge of the covering having a tricurve profileto fit sclera and an ablated cornea as in FIG. 1J5;

FIG. 1K shows a covering having fenestrations on an outer portion topass a medicament when the cornea is sealed, in accordance withembodiments of the present invention;

FIG. 1L shows fitting of a covering to a cornea in accordance withembodiments as described herein;

FIG. 1M shows deflection of a portion of a covering in response to anepithelial irregularity so as to smooth the irregularity, in accordancewith embodiments as described herein;

FIG. 1N shows a test apparatus to measure deflection of a portion of alens in response to a load, in accordance with embodiments as describedherein;

FIG. 2A shows surgical placement of a covering on an eye having anepithelial defect with an applicator, in accordance with embodiments ofthe present invention:

FIG. 2A1 shows a surgeon's view of the eye through the applicator as inFIG. 2A;

FIG. 2A2 shows a patient's view of a fixation light through theapplicator as in FIG. 2A;

FIG. 2B shows a covering coupled to an applicator for placement on acornea as in FIG. 2A, in accordance with embodiments of the presentinvention;

FIG. 2C shows an applicator coupled to a covering with block adhesionand peeling of the covering from the applicator with a movablecomponent, in accordance with embodiments of the present invention;

FIG. 2C1 shows an applicator coupled to a covering with foam to adherethe covering to the applicator when dry and application of a liquid torelease the covering from the applicator when wet, in accordance withembodiments of the present invention;

FIG. 2D shows an applicator as in FIG. 2A coupled to a covering;

FIG. 2D1 shows a covering coupled to an applicator with adhesion, inaccordance with embodiments of the present invention;

FIG. 2E shows an applicator comprising a rigid component and a flexiblecomponent, in accordance with embodiments of the present invention;

FIG. 2E1 shows coupling of a covering to an applicator as in FIG. 2E, inaccordance with embodiments of the present invention;

FIG. 2F shows an applicator and a covering as in FIG. 2E with theapplicator in an expanded configuration to position the covering on thecornea, in accordance with embodiments of the present invention;

FIG. 2G shows an applicator and a covering with the covering held in achannel of the applicator, in accordance with embodiments of the presentinvention;

FIG. 2H shows an applicator and a covering with the applicatorcomprising an extension to deliver the covering, in accordance withembodiments of the present invention;

FIG. 2I shows an applicator and a covering with the applicatorcomprising a slider to release the covering, in accordance withembodiments of the present invention;

FIG. 2J shows an applicator and a covering with the applicatorcomprising a hinge to release the covering, in accordance withembodiments of the present invention;

FIG. 2K1 and 2K2 show side and top views, respectively, of an applicatorand a covering with the applicator comprising a compressed structurethat is released so as to deliver the covering to the cornea, inaccordance with embodiments of the present invention;

FIG. 2K3 shows the applicator as in FIGS. 2K1 and 2K2 in a releasedconfiguration to deliver the covering to the cornea, in accordance withembodiments of the present invention;

FIG. 3A shows an applicator comprising extensions coupled to pads todeliver the covering, in accordance with embodiments of the presentinvention;

FIG. 3B shows an applicator comprising roller pads to deliver thecovering, in accordance with embodiments of the present invention;

FIG. 3C shows concave roller pads for use with an applicator as in FIG.3B, in accordance with embodiments of the present invention;

FIG. 3D shows delivery of a covering to the cornea with an applicatorcomprising rollers as in FIG. 3B, in accordance with embodiments of thepresent invention;

FIG. 4A shows an applicator comprising a fixation ring coupled to acovering, in accordance with embodiments of the present invention;

FIG. 4B shows a side view of the applicator as in FIG. 4A;

FIG. 5A shows an apparatus comprising a covering and applicator storedin a substantially dry, sterile compartment of a container, inaccordance with embodiments of the present invention;

FIG. 5B shows an apparatus comprising a covering and applicator storedin a substantially moist, sterile compartment of a container, inaccordance with embodiments of the present invention;

FIGS. 5B1 and 5B2 shows an apparatus 530 comprising covering 100 and anapplicator 200 stored in a sterile compartment of a container, in whichthe container comprises a support surface 534 with the covering 100disposed thereon in a channel 532 sized to receive the applicator 200.The channel 532 can guide the applicator onto the covering when thecovering is advanced in the channel to couple to the applicator. Thecovering can be positioned on the cornea with the applicator.

FIG. 5B3 shows an applicator with a support coupled to a handle with ajoint disposed between the support and the handle to move the handlewhen the support is coupled to the eye, in accordance with embodimentsof the present invention;

FIG. 5C1 shows an apparatus comprising a removal tool, in accordancewith embodiments of the present invention;

FIG. 5C2 shows the distal portion comprising the tip of the removal toolas in FIG. 5C1.

FIG. 5C3 shows the apparatus of FIG. 5C1 aligned with the patient;

FIG. 5C4 shows the long dimension 568L of the cross section of theopening of tip 568 aligned substantially with a plane of the pupil and aperipheral temporal portion of the covering when the handle ispositioned near the temple of the patient;

FIG. 5D shows a cannula of the apparatus as in FIG. 5C1 inserted underthe covering;

FIG. 6 shows a mold to form a covering and comprising a solid an innercomponent placed therein prior to injection of a flowable material, inaccordance with embodiments of the present invention;

FIG. 6A shows a mold to form a covering and having a solid innercomponent comprising a rigid material placed therein prior to injectionof a flowable material, in accordance with embodiments of the presentinvention;

FIG. 7 shows a method of manufacturing a covering with a mold as in FIG.6, in accordance with embodiments of the present invention;

FIG. 8 shows a method of placing a covering on a cornea of an eye, inaccordance with embodiments of the present invention;

FIG. 9 shows a method of removing a covering from a cornea of an eye, inaccordance with embodiments of the present invention;

FIG. 10A shows corneal topography and smoothing of epithelialirregularities with the covering, in accordance with embodiments of thepresent invention;

FIGS. 10B, 10C and 10D show, horizontal, vertical and central OCTimages, respectively, of the covering on the eye of FIG. 10A without agap disposed between the covering and the cornea such that the coveringdirectly contacts the ablated stroma and regenerating epithelium;

FIGS. 11A1A to 11A1D show OCT images of portions of the soft coveringfrom, respectively, the superior portion of the covering, the nasalportion of the covering, the temporal portion of the covering and theinferior portion of the covering at 48 hours post-op on the right eye(OD);

FIGS. 11A2A to 11A2D show OCT images of portions of the soft coveringfrom, respectively, the superior portion of the covering, the nasalportion of the covering, the temporal portion of the covering and theinferior portion of the covering at 48 hours post-op on the left eye(OS);

FIGS. 11A3A to 11A3D show OCT images of portions of the soft coveringfrom, respectively, the superior portion of the covering, the nasalportion of the covering, the temporal portion of the covering and theinferior portion of the covering at 72 hours post-op on the right eye(OD);

FIGS. 12A1A to 12A1C show OCT images of portions of the rigid coveringfrom, respectively, the temporal portion of the covering, the nasalportion of the covering and the inferior portion of the covering at 24hours post-op on the right eye (OD);

FIGS. 12A2A to 12A2D show OCT images of portions of the rigid coveringfrom, respectively, the superior portion of the covering, the temporalportion of the covering, the nasal portion of the covering and theinferior portion of the covering at 48 hours post-op for on the left eye(OS); and

FIGS. 12A3A to 12A3D show OCT images of portions of the rigid coveringfrom, respectively, the superior portion of the covering, the temporalportion of the covering, the nasal portion of the covering and theinferior portion of the covering at 72 hours post-op on the left eye(OS).

DETAILED DESCRIPTION OF THE INVENTION

Embodiments of the present invention as described herein can be combinedwith the therapeutic covering device for pain management and vision asdescribed in U.S. patent application Ser. No. 12/384, 659, filed Apr. 6,2009, entitled “Therapeutic Device for Pain Management and Vision”, thefull disclosure of which is incorporated herein by reference andsuitable for combination in accordance with some embodiments of thepresent invention as described herein.

The embodiments described herein can be used to treat eyes in many wayswith a covering. Although specific reference is made to treatingepithelial defects of the eye, the covering described herein can be usedfor long term vision correction with extended wear contact lenses thatinhibit swelling of the cornea when the covering is positioned on theeye for an extended period.

The coverings as described herein can seal the cornea, so as to restoredeturgescence of the cornea to decrease pain and improve vision. Thecovering can be configured in many ways to seal the cornea, and thecovering comprises a substantially oxygen permeability to promote growthof the epithelium and to guide the growth of the epithelium such thatthe epithelium regenerates smoothly for patient vision. The restorationof the deturgescence of the cornea can decrease irregularities of thecornea such as ablated stromal irregularities, for example centralislands. The sealing of the cornea with the environment to promoteepithelial regeneration can result in improved epithelial smoothness andan improved profile of the ablated stromal surface under theregenerating epithelium.

In many embodiments, the covering comprises an at least partiallyconformable portion, such that the at least partially conformableportion can one or more of match or grossly approximate the correctedcorneal curvature to as to provide vision of at least about 20/30, andsuch that the at least partially conformable portion substantially doesnot conform to the corneal irregularities caused by epithelial healingand edema, such as irregularities of the epithelium and central islandsthat may appear post-ablation in ablated eye.

In many embodiments, the at least partially conformable portion of thecovering can be configured so as to conform at least partially to theepithelium when the covering is positioned on the epithelium so as todeflect the epithelium.

The epithelium can conform to the covering so as to seal the covering,for example with deformation of the epithelium such as with one or moreof indentation or overgrowth of the epithelium around a perimeter of thecovering.

In many embodiments, the curvature of the covering can matchsubstantially the profile of the ablated region, so as to providevisions of at least about 20/30 when positioned on the cornea.

As used herein, mathematical equations and scientific notation can beused to values in many ways understood by a person of ordinary skill inthe art, for example so as to express data in accordance with notationsused in many commercially available spreadsheets such as Excel™commercially available from Microsoft. As used herein the symbol “E” canbe used to express an exponent in base 10, such that 1E1 equals about10, 2E1 equals about 20, and 4E2 equals about 400. As used herein thesymbol “̂” can be used to express an exponent, such that ÂB equals A^(B).Units can be expressed in many ways and as would be understood by aperson of ordinary skill in the art, for example “m” as meters, “Pa” asthe Pascal unit for pressure, “MPa” as Mega Pascal.

FIG. 1 shows an eye 2 suitable for incorporation of the covering 100 asdescribed herein. The eye has a cornea 10 and a lens 4 configured toform an image on the retina 5, and the image can form on a fovea 5Fcorresponding to high visual acuity. The cornea can extend to a limbus 6of the eye, and the limbus can connect to a sclera S of the eye. The eye2 has a pars plana PP located near limbus 6. A conjunctiva C of the eyecan be disposed over the sclera. The lens can accommodate to focus on anobject seen by the patient. The eye has an iris 8 that defines a pupil 9that may expand and contract in response to light. The eye alsocomprises a choroid CH disposed the between the sclera 7 and the retina5. The eye has a vitreous humor VH extending between the lens and theretina. The retina 5 senses light of the image and converts the lightimage to neural pulses that are processed and transmitted along an opticnerve ON to the brain of the patient.

FIG. 1-1A shows an ablated eye immediately following refractive surgery,for example PRK surgery resulting in an epithelial defect. The eye 2comprises an iris 8 that defines a pupil 9, through which light passessuch that the patient can see. Cornea 10 includes an epithelium 12disposed over a stroma 16. The epithelium 12 comprises a thickness 12Tthat can be about 50 um. A tear liquid covers the anterior surface ofepithelium 12. In at least humans, primates and some birds, a Bowman'smembrane 14 is disposed between epithelium 12 and stroma 16. Bowman'smembrane 14 comprises an acellular substantially collagenous tissue witha thickness of about 5 to 10 microns. Stroma 16 comprises asubstantially collagenous tissue with keratocytes disposed therein. Insome animals, Bowman's membrane may be absent and the epithelium may bedisposed adjacent to the stromal layer. An endothelium 18 is disposedunder stroma 16. Endothelium 18 comprises a layer of cells that pumpwater from cornea 10 toward iris 8. Tear liquid also covers surfaces ofthe cornea that are exposed by the epithelial defect, such as an exposedsurface of Bowman's membrane and an exposed stromal surface.

In a normal healthy eye, epithelium 12 is disposed across cornea 10 andis a protective layer. Epithelium 12 covers nerves of the cornea andminimizes the flow of water from the tear film of the eye to into thestroma. Epithelium 12 in most human patients can be about 40 to 60microns thick, for example about 50 microns. When epithelium 12 isintact, endothelium 18 can pump water from stroma 16 and maintainhydration in the cornea at a proper level. The mechanism by which thestroma of the cornea remains properly hydrated can be referred to asdeturgescence. Deturgescence of the cornea can be important becauseexcess hydration of the cornea can result in swelling of the cornea andlight scattering, or haze, that can degrade vision. The total thicknessof normal cornea 10 from endothelium 18 to tear liquid in most humanpatients can be from about 400 to 600 microns. A healthy cornea withnormal hydration comprises about 80 to 85% water. Edema of the corneadue to swelling of the cornea, for example with additional water, canincrease the thickness of the cornea.

With refractive surgery, for example PRK, the epithelium can be removedto ablate a refractive correction into Bowman's membrane 14 and/orstroma 16. An initial profile of the anterior surface of stroma and/orBowman's membrane is ablated to an ablated profile 20 to correct thepatient's vision. The profile of tissue removed to correct vision isdescribed in U.S. Pat. No. 5,163,934, entitled “Photorefractivekeratectomy”, the disclosure of which may be suitable for combination inaccordance with some embodiments of the present invention describedherein. Ablated profile 20 generally comprises an optical zone thatextends across the cornea to correct refractive error of the eye and maycorrect aberrations of the eye, for example wavefront aberrations.Ablated profile 20 is bounded by boundary 20B that may circumscribe theablated profile. The ablation profile 20 comprises a maximum dimensionacross, for example a diameter 20D.

The epithelium may comprise an inner boundary that moves centripetallyinward as indicated by arrows 30

FIG. 1-1B shows an ablated eye about 1 to 2 days following refractivesurgery resulting in an epithelial defect. The epithelium has at leastpartially covered the ablation. The epithelium may compriseirregularities and an inner boundary that moves centripetally inward asindicated by arrows 30. The thickness profile 12RP of the regeneratingepithelium 12R can be irregular and degrade vision. The inner portion ofthe epithelium near the boundary may comprise a height greater than anouter portion of the epithelium away from the boundary of theepithelium. The portion of the ablation not covered with the epitheliumand the inner portion of the epithelium near the boundary can result inaberrations, for example aberrations corresponding to a meniscus of thetear and a far sighted portion of the cornea. As variation in epithelialhealing among individuals can be observed, the epithelial defect of atleast some individuals can be present at 2 and 3 days post-op, withcorresponding aberrations.

FIG. 1-1C shows an ablated eye when the epithelium has regeneratedfollowing refractive surgery resulting in an increased epithelialthickness centrally when the epithelium has regenerated, for example atabout 3 days post-op. The regenerating epithelium may have anirregularity 12I, for example corresponding to an increased elevation ofan inner portion of the epithelium near the center of the ablation, forexample. Work in relation to embodiments as described herein suggeststhat the natural regeneration of the epithelium can provide an innerportion having an increased central elevation with optical power thatmay correspond to about 1 to 3 Diopters of additional optical power. Theregenerating epithelium comprises a thickness profile 12RP extendingalong the surface of Bowman's membrane 14 and the ablation 20. With PRKthe thickness profile 12RP of the epithelium can regenerate for at leastone week, for example one month, such that vision can be degraded whenthe thickness profile 12RP of the epithelium regenerates, and PRKsurgery of the cornea can be combined in accordance with embodimentsdescribed herein so as to improve vision.

In many embodiments as described herein, irregularities of the corneaare decreased when the epithelium regenerates so as to provide one ormore of improved vision or comfort. The coverings as described hereincan be configured so as to decrease an effect on vision of cornealirregularity 12I, decrease the height profile of irregularity 12I,decrease transfer of irregularity 12I to an anterior surface of thecovering, smooth irregularity 12I with the covering, regenerateepithelium 12 such that irregularity 12I is decreased, or combinationsthereof. In many embodiments, the covering 100 as described herein canbe placed on the eye such that a smooth layer 12S of regeneratedepithelium 12R substantially covers the ablated profile so as to provideimproved vision sooner than would occur without covering, for example atabout 3 to 4 days post-op with PRK. In many embodiments, the coveringcan provide an environment 100E as described herein so as to guideepithelial regeneration and smooth the regenerated epithelium.

In many embodiments, the cornea 10 of an eye 2 has an epithelial defect11 following refractive surgery such as PRK, and a covering 100positioned over the epithelial defect 11.

FIG. 1-2A shows a covering 100 positioned on cornea 10 an eye 2 havingan epithelial defect 11, in which the covering abuts the cornea to sealthe cornea. The covering may comprise a curved body, for example acurved contact lens body shaped to fit the cornea.

The covering 100 can be sized to cover the ablated profile andepithelial defect. The inner portion 110 comprises a dimension across102 that can be sized to extend across a majority of the ablation, andthe outer portion 120 comprises a dimension across 104 sized to extendacross at least the epithelial defect and contact the epithelium onopposite sides of the defect.

The dimension 102 extending across a majority of the ablation may extendabout 6 to 8 mm, for example, and may be sized larger than the ablation.The dimension 104 may comprise about 12 to 14 mm across, for example soas to extend to the limbus and can be sized to the limbus of the patientfor example. Work in relation to embodiments suggests that the coveringsized to extend to the limbus and circumferentially around the limbuscan be centered on the cornea. The covering may extend such that theouter rim of the covering contacts the conjunctiva disposed above thesclera peripheral to the limbus, for example, and that suchconfigurations may center the lens on the cornea, for example.

The thickness of the covering can be sized and shaped in many ways. Theinner portion 110 of the covering comprises a thickness 106 and theouter portion 120 of the covering comprises a thickness 108. Thethickness 106 of the inner portion may comprise a substantially uniformthickness such that the inner portion comprises an optical power of nomore than about +/−1D prior to placement on the eye, for example whenheld in front of the eye and separated from the cornea by a distance.Alternatively, the thickness of the inner portion may vary so ascomprise optical power, for example optical power to correct vision ofthe patient.

FIG. 1-2B shows a smooth layer 12S of regenerated epithelium 12Rsubstantially covering an ablated profile. The environment 100E isconfigured to guide epithelial regeneration and smooth the regeneratedepithelium. The regenerating epithelium comprises a thickness profile12RP.

The epithelium grows centripetally from circumscribing boundary 12Etoward the center of ablated profile 20 to cover the exposed stroma, asindicated by arrows 30.

The covering 100 may comprise an inner portion 110 and an outer portion120. The outer portion 110 can be configured to form a seal 100S withthe cornea near the edge of the ablation and the epithelial defect, forexample with a soft conformable material such as silicone or siliconehydrogel. The inner portion 120 is positioned over the pupil andconfigured for the patient to see, and may comprise a rigidity greaterthan the outer portion, so as to smooth irregularities of the epitheliumwhen the cornea heals. Alternatively, the inner portion may comprise arigidity equal to or less than the rigidity of the outer portion aswell. For example, the inner portion may comprise silicone and the outerportion may comprise silicone, and the inner portion may comprise one ormore of a more rigid silicone or a greater thickness such that the innerportion can be more rigid than the outer portion so as to smooth theepithelium. Although the inner portion can be more rigid than the outerportion, the inner portion is sufficiently soft, flexible andconformable so as to conform at least partially to the ablated profile20 in the stroma, such that the patient receives the benefit of thevision correction with the ablation profile 20 when the patient looksthrough the inner portion and the inner portion smoothes the epithelium.Work in relation to embodiments of the present invention suggests thatthe regenerating epithelium is softer than the underlying stroma ofablation profile 20, such that the inner portion can be configured toconform to the shape of the ablation profile 20 when the inner portionsmoothes the epithelium disposed under the inner portion.

The covering 100 may comprise one or more of many optically clearmaterials, for example synthetic materials or natural material suchcollagen based materials, and combinations thereof, such as described inU.S. patent application Ser. No. 12/384, 659, filed Apr. 6, 2009,entitled “Therapeutic Device for Pain Management and Vision”, U.S. Pub.No. US 2010-0036488 A1, published on 11 Feb. 2010. For example, the lensmaterial may comprise a naturally occurring material, such as collagenbased material. Alternatively or in combination, the lens material maycomprise a known synthetic material, for example hydroxyethylmethacrylate (HEMA) hydrogel, hydrogel, silicone, for example hydratedsilicone and derivatives thereof. For example the optically clearmaterial may comprise one or more of silicone, silicone hydrogel,silicone comprising resin, silicone comprising silicate, acrylate,collagen. The cured silicone may comprise silicone that is two-part heatcured and RTV (room temperature vulcanized). For example, polydimethylsiloxane such as NuSil, or poly(dimethyl) (diphenyl) siloxane may beused to mold the covering, for example with less than 10% water contentso as to increase oxygen diffusion through the covering. The covering100 may comprise perfluoropolyethers or fluorofocal. The lens materialcan be elastic, for example a stretchable elastic material such assilicone, such that the lens can seal the cornea. The lens material canbe cured with a hardness and size and shape such that the coveringcomprises a modulus within a range from about 4 to about 20 MPa. Thematerial may comprise, for example, silicone elastomer having opticallyclear silicate disposed therein and a water content of no more thanabout 10%, for example no more than about 5%, such that the lenscovering has a very high Dk exceeding 150, and the silicone lenscomprising silicate can be treated to provide a wettable surface. Thelens may comprise hydrogel, for example silicone hydrogel, and can beformed with a water content within a range from about 5% to about 35%and a modulus within a range from about 4 to about 20 MPa, such that thecovering conforms at least partially to the ablated stroma.

The covering may comprise silicone or silicone hydrogel having a lowionoporosity such that covering seals to the cornea. For example,covering may comprise silicone hydrogel comprising a low ionpermeability, and the range of water can be from about 5% to about 35%,such that the Dk is 100 or more. The low ion permeability may comprisean Ionoton Ion Permeability Coefficient of no more than about 0.25×10−3cm2/sec so as to seal the cornea, for example no more than about0.08×10−3 cm2/sec. The low ion permeability comprises an Ionoton IonPermeability Coefficient of no more than about 2.6×10−6 mm2/min to sealthe cornea, for example no more than about 1.5×10−6 mm2/min.

The covering 100 may comprise a wettable surface coating 130 disposed onat least the upper side of the covering, such that the tear film of thepatient is smooth over the covering and the patient can see. Thewettable surface coating may comprise a lubricious coating for patientcomfort, for example to lubricate the eye when the patient blinks. Thewettable coating may comprise a contact angle no more than about 80degrees. For example the coating may comprise a contact angle no morethan about 70 degrees, and the contact angle can be within a range fromabout 55 to 65 degrees to provide a surface with a smooth tear layer forvision. For example, the wettable coating can be disposed both an uppersurface and a lower surface of the covering. Alternatively, the lowersurface may comprise a hydrophobic surface material and the lowerhydrophobic surface may comprise the inner portion 110 and the outerportion 120. At least the outer portion 120 may comprises a lowersurface composed of a sticky, tacky, material, for example a hydrophobicmaterial. The inner portion may also comprise the lower surfacecomprised of the sticky, tacky, hydrophobic material. The upper surfacemay comprise the wettable coating extending over at least the innerportion 110.

The wettable coating may comprise one or more of many materials. Forexample, the wettable coating may comprise polyethylene glycol (PEG),and the PEG coating can be disposed on Parylene™. Alternatively, thewettable coating may comprise a plasma coating, and the plasma coatingcomprise a luminous chemical vapor deposition (LCVD) film. For example,the plasma coating comprises at least one of a hydrocarbon, for exampleCH4, O2 or fluorine containing hydrocarbon, for example CF4 coating.Alternatively or in combination, the wettable coating may comprise apolyethylene glycol (PEG) coating or 2-hydroxyethylmethacrylate (HEMA).For example, the wettable coating may comprise HEMA disposed on aParylene™ coating, or the wettable coating may compriseN-vinylpyrrolidone (NVP) disposed on a Parylene™ coating.

The covering 100 may comprise a lower surface corresponding to one ormore of many suitable shapes to fit the covering to the cornea. Forexample, the lower surface of the covering may correspond to base radiusof curvature. With post ablation corneas, the covering can conformsubstantially to the cornea. The covering may comprise a second curve incombination with a first curve, such that the lower surface comprises abicurve surface. Alternatively, the lower surface may correspond to anaspheric surface. For example an aspheric surface may comprise an oblateshape and conic constant to fit a post PRK eye. Also, it may be helpfulto fit the covering to the cornea, for example with selection of onecovering from a plurality of sizes.

FIG. 1A shows the covering 100 having the thickness 108 of the outerportion sized such that the outer portion can conform to the epithelium.The thickness of the outer portion can be substantially constant, or mayvary as described herein below.

FIG. 1A1 shows covering 100 positioned on an eye and blinking of theeye. An upper lid and a lower lid can blink over the eye. Work inrelation to embodiments suggests that the upper lid can exert a downwardmovement 20 and that the lower lid can exert an upper movement 22 on theeye. The downward movement 20 can be greater than the upper movement 22.The wettable coating material as described herein can decrease force andmovement transferred from the lids to the covering so as to inhibitmotion of the covering. The downward movement 20 greater than the upwardmovement 22 can effect epithelial growth near the perimeter of covering100.

FIG. 1B1 shows covering 100 as in FIG. 1-2A prior to placement on thecornea. The covering 100 may comprise a base radius R1 of curvature, andthe base radius of curvature may be slightly shorter than the ablatedcornea such that the covering can be steeper than the cornea prior toplacement on the cornea. The covering 100 comprises a firstconfiguration 100C1 prior to placement on the cornea.

The base radius R1 can be sized to the cornea in many ways. For examplebase radius R1 may have a radius corresponding to the outer unablatedportion of the cornea. Alternatively or in combination, the base radiusR1 may have a radius corresponding to the post ablated eye.

The covering 100 may comprise a modulus within a range from about 4 MPato about 20 MPa, such that central portion can conform at leastpartially to the ablated stroma and so that the covering can smoothcorneal irregularities and stromal irregularities of the ablated cornea.The covering may comprise an elastomeric stretchable material such thatthe covering can stretch to fit the cornea, for example. The coveringhaving the modulus within a range from about 4 MPa to about 20 MPa canbe formed in many ways as described herein. For example, the coveringmay comprise a single piece of material having a substantially uniformthickness extending across the ablated cornea and at least a portion ofthe unablated cornea, and the single piece of material may comprise anelastic material such as a silicone elastomer or a hydrogel.Alternatively, the covering may comprise a single piece of materialhaving a non-uniform thickness extending across the ablated cornea andat least a portion of the unablated cornea. The covering can be shapedin many ways and may comprise a single piece of one material, or maycomprise a single piece composed to two similar materials, or maycomprise a plurality of materials joined together.

The covering 100 may comprise one or more outer portions extendingoutside the inner central, and these outer portions may seal the corneawhen the inner portion conforms at least partially to the ablatedstroma. For example, the covering 100 may comprise outer portionadditional shapes disposed outward from a central portion as describedherein. For example, the covering may comprise a bicurve having a secondradius of curvature disposed peripheral to the inner radius R1 ofcurvature to fit the unablated portion of the cornea. For example, thesecond and outer radius of curvature may comprise a shorter radius ofcurvature when the central portion is treated for myopia. The coveringmay comprise a third radius of curvature longer than the second radiusof curvature so as to fit the sclera under the conjunctiva. The coveringmay comprise an oblate shape to fit the ablated and non-ablated portionsof the cornea, and the covering may extend over the sclera with an outerportion, for example.

FIG. 1B2 shows the covering as in FIG. 1B1 conforming to ablated stromaltissue and smoothing the epithelium over the ablated stroma. The corneacomprises an ablated surface 20 to correct vision that may have acorresponding radius of curvature, for example radius R2. The ablatedprofile 20 may comprise additional, alternative, or combinational shapeswith those corresponding to radius R2, such as aberrations ablated intothe cornea to correct aberrations of the eye and astigmatism ablatedinto the cornea, and the inner portion 110 of covering 100 can conformto these ablated profiles of the cornea such that the patient canreceive the benefit of the ablative vision correction when the coveringis positioned on the cornea. For example, the cornea ablation profile 20may correspond to radius of curvature R2, and the inner portion 110 canflatten from configuration 100C1 corresponding to radius of curvature R1prior to placement to a second configuration 100C2 correspondingsubstantially to the ablated profile 20, such the patient can see withthe benefit of ablation profile 20. For example, the secondconfiguration 100C2 can comprise a conforming radius of curvature R12that corresponds substantially to radius of curvature R2. The profilecorresponding to the first configuration 100C1 of the covering 100 isshown positioned over cornea 10 to illustrate the change in profile ofthe covering from configuration 100C1 prior to placement to conformingconfiguration 100C2 of the covering 100 when positioned on the cornea.

The conformable covering 100 comprises sufficient rigidity so as tosmooth the epithelium when covering 100 is positioned on the cornea overthe ablation profile 20. The epithelium comprises a peripheral thickness12T that may correspond substantially to a thickness of the epitheliumprior to debridement of the epithelium to ablate the cornea. Theepithelium also comprises regenerating epithelium 12R disposed over theablation profile 20. The covering 100 can smooth the epithelium 12R whenconforming to the cornea in the second configuration 12C2. For example,irregularities 12I of the regenerating epithelium 12R disposed over theablation can be smoothed when the epithelium regenerates along the innerportion of covering 100, such that the irregularities 12I of theregenerating epithelium 12R are thinner than the thickness 12T of theperipheral epithelium.

Work in relation to the embodiments as described herein indicates thatan at least partially conformable covering having a modulus within arange from about 4 MPa to about 20 MPa can conform at least partially tothe ablated stroma and smooth irregularities of the epithelium andstroma so as to improve vision as described herein. The covering havingthe modulus within the range from about 4 MPa to about 20 MPa can beformed in many ways as described herein.

The conformable covering 100 may comprise a perimeter 120P with arigidity sufficient to indent the epithelium along at least a portion ofthe perimeter so as to seal the cornea with seal 100S. The portion 12Cof the epithelium 12 can extend over the perimeter of the covering 120P.

FIG. 1B2A shows a covering as in FIG. 1B2 forming an indentation 12I inthe epithelium such that the epithelium 12 extends over at least aportion of the perimeter 120P of the covering. The covering formsindentation 12I in the epithelium such that the epithelium comprises anindentation thickness 121T that is less than an outer thickness of theepithelium 12T. The indentation of the epithelium with the covering canhelp to seal the cornea with the perimeter.

FIG. 1B2B shows a covering as in FIG. 1B2 forming indentation 12 in theepithelium. The covering forms indentation 12I in the epithelium suchthat the epithelium comprises an indentation thickness 121T that is lessthan an outer thickness of the epithelium 12T. The indentation of theepithelium with the covering can help to seal the cornea with theperimeter.

Work in relation to embodiments described herein suggests theindentation of the covering can vary radially around the eye of thepatient, in accordance with orientation of the covering on the eye whenthe covering comprises a substantially constant rigidity of the outerportion, for example a substantially constant rigidity around theperimeter. The inferior portion of the covering may comprise a greateramount of epithelial covering over the perimeter than the superiorportion of the covering. For example, FIG. 1B2A may correspond to afirst portion of covering 100 at an inferior location of the cornea andFIG. 1B2B may correspond to a second portion of the covering at asuperior location of the cornea. Work in relation to embodiments alsosuggests that there may be variability in covering of the perimeter withthe epithelium between the nasal portion of the perimeter, and thetemporal portion of the perimeter, although both the nasal and temporallocations can comprise covering intermediate and between the moreextensive covering of the inferior portion and the less extensivecovering of the superior portion of the perimeter.

FIG. 1B2C shows a covering abutting the cornea to seal the corneawithout forming a substantial indentation in the epithelium. Thecovering may comprise a chamfer to contact and seal the cornea. Therigidity of the outer portion can be determined based on the thicknessof the outer portion of the covering, hardness of the material, andchamfer angle so as to contact the epithelium to seal the cornea withoutsubstantial deformation of the epithelium.

The covering may comprise a non-uniform rigidity around the outerportion of the covering comprising the perimeter. For example, thecovering may comprise a superior portion corresponding to a superiorlocation on the cornea and an inferior portion corresponding to aninferior location on the cornea. The superior portion may comprise arigidity less than the inferior portion. For example, the superiorportion may comprise the rigidity less than the inferior portion, suchthat deformation of the epithelium is inhibited when the perimeter abutsthe cornea is sealed. Alternatively, the superior portion may comprisethe rigidity less than the inferior portion such the deformation of theepithelium with the covering comprises a substantially constant amountaround the perimeter, for example a deformation of no more than about 10um, for example 5 um.

FIG. 1C shows a therapeutic covering as in FIG. 1-2A comprising acovering molded with a homogeneous material, in which the outer portioncomprises a thickness configured to conform with the cornea and in whichthe inner portion 110 comprises thickness configured to smooth theepithelium and conform to the ablated profile 20. The outer portion 120may comprise a thickness of no more than about 100 microns. For examplethe outer portion 120 may comprise a thickness of about 50 microns atthe boundary with the inner portion 110, and linearly taper from 50microns at the boundary with the inner portion to about 20 microns atthe periphery of the outer portion 120. The inner portion 110 maycomprise a thickness of no more than about 250 microns, for example nomore than about 200 microns. For example, the inner portion may comprisea thickness of about 100 microns. For example, the thickness of each ofthe inner portion and the outer portion may comprise no more than about50 microns so as to provide substantial oxygen transport and epithelialregeneration. Many materials can be used as described herein, and thecovering may comprise one or more materials. For example, the coveringmay comprise a single piece of material such as silicone having a watercontent within a range from about 0.1% to about 10%, for example no morethan about 1%, and a hardness Shore A durometer parameter within a rangefrom about 5 to about 90, for example within a range from about 40 toabout 85.

FIG. 1C1 shows a covering 100 having an inner portion 110 comprising aninner thickness and an inner material 110M and an outer portion 120comprising an outer thickness and an outer material 120M, in which theinner thickness is greater than the outer thickness. The inner material110M may comprise many materials and may comprise an optically clearsilicone, for example silicone with resin. The inner material maycomprise silicone positioned in a mold with the outer portion 120 formedaround the inner portion. The inner portion may comprise a hardnesssimilar to the outer portion. The outer material 120M of the outerportion 120 may comprise a material similar to the inner portion. Forexample the outer material 120M may comprise silicone and the innermaterial 110M may comprise silicone. This use of similar materials onthe inner and outer portion can improve adhesion of the inner portion tothe outer portion. The outer material 120M may extend along the innerportion 110, for example along the underside of the inner portion 110,such that the inner material 110M is held in a pocket of the outermaterial 120M. Alternatively, the inner material 110M may extendsubstantially across the thickness of the inner portion 110, such thatthe outer material 120M comprises a substantially annular shape with theinner material 110M comprising a disc shaped portion disposed within theannulus and extending substantially from the upper surface coating tothe lower surface coating when present.

FIG. 1C1A shows a covering as in FIG. 1C1 adhered to the cornea with asmooth upper surface, and a lower surface conforming to irregularity ofthe cornea, for example an irregularity comprising a central island CIof the ablated stroma. The central island CI may comprise an outwardprotrusion in the ablated profile of the stroma at least about 1 micronoutward and about 2.5 mm across, for example. The upper surface maycomprise a substantially rigid material for vision correction, and thelower surface may comprise a soft material so as to deflect toirregularities of the cornea when the upper surface provides opticalcorrection. For example the lower surface may comprise an indentation110I when positioned on the irregularity of the cornea. Although thelower surface comprising the soft material can deflect to correspond tothe ablation profile 20, the upper surface comprising the rigid materialmay comprise a predetermined curvature selected by a health careprovider so as to fit the ablation profile and correspond to therefractive correction of the patient so as to provide vision correction.

FIG. 1C2 shows a covering as in FIGS. 1-2A to 1B2 having inner portion110 comprising an inner thickness and inner material 110M and outerportion 120 comprising an outer thickness and outer material 120M, inwhich the inner thickness can be greater than the outer thickness andthe outer material 120M extends around the inner material 110M. Thecovering 100 may comprise at least a bicurve covering having at least asecond radius RIB. The inner portion 110M may comprise three layers ofmaterial, a first layer 110L1 of a first material 110M1, a second layer110L2 of a second material 110M2 and a third layer 110L3 of a thirdmaterial 110M3. The second material 110M2 may comprise a rigid material,for example one or more of a rigid gas permeable material, a rigidsilicone, or a rigid silicon acrylate. The first material 110M1 and thethird material 110M3 may comprise a soft material, for example a softelastomer or soft hydrogel such as one or more of a soft optically clearsilicone or a soft silicone hydrogel. The first material, the thirdmaterial, and the outer material 120M may comprise similar materials,such that the second layer of rigid material 110M2 is encapsulated withthe first soft material 110M1, the third soft material 110M3 and on theperimeter with the soft outer material 120M. In many embodiments, thesecond rigid material 110M2 comprises a material similar to each of thefirst material 110M1, the third material 110M3 and the outer material120M, for example each may comprise silicone, such that thecorresponding portions of the covering 100 can be bonded together withthe silicone similar silicone elastomer material, for example. In manyembodiments, the covering 100 can be formed in a mold with rigid secondmaterial 110M2 placed in the mold and encapsulated within a single pieceof material comprising first material 110M1, third material 110M3 andouter material 120M, such that first material 110M1, third material110M3 and outer material 120M comprise substantially the same material,for example silicone elastomer. The rigid second material 110M2 maycomprise silicone bonded to each of first material 110M1, third material110M3 and the outer material 120M, for example with curing such thatfirst material 110M1, third material 110M3 and outer material 120Mcomprise the same soft silicone material bonded to the second material110M2 comprising rigid silicone.

The soft material comprising soft outer portion 120 composed of softmaterial 120M, first layer 110L1 composed of soft material 110M1 andthird layer 110L3 composed of soft material 120M3 can provide improvedcomfort and healing for the patient. The soft material can deflect, bendor indent so as to conform at least partially to the tissue of the eyewhen the rigid portion comprising rigid material 110M2 corrects visionof the patient. The dimension 102 across inner portion 110 can be sizedto substantially cover the ablation zone and slightly smaller than theablation dimensions, such as ablation diameter 20D, so that theepithelium can grow inward and contact the layer 110L1 of soft firstmaterial 110M1 without substantial disruption from the rigid material120M2 when the inner portion 110M corrects vision with the layer ofrigid material 110M2. The eyelid can also move over the third layer110M3 for improved comfort. The soft first material 110M1 and soft thirdmaterial 110M3 may comprise soft elastomer or soft hydrogel, forexample, and may each comprise the same material so as to encapsulatethe second layer 110L2 of rigid second material 110M2.

The soft material comprising soft outer portion 120 composed of softmaterial 120M, first layer 110L1 composed of soft material 110M1 andthird layer 110L3 composed of soft material 120M3 can have a moduluswithin a range from about 1 to 20 MPa, for example within a range fromabout 1 to 5 MPa.

The material inner material 120M and 120M2 of second layer 120L2 canhave a modulus within a range from about 5 to about 35 or more, forexample as set forth in Table A below. For example, when material 120Mcomprises silicone elastomer or layer 110L2 of material 120M2 comprisessilicone elastomer, the modulus can be within a range from about 5 toabout 35 MPa, for example within a range from about 20 to about 35 MPa.

The layers of covering 100 can comprise dimensions so as to providetherapeutic benefit when placed on eye 2. The thickness of layer 110L1can be from about 5 um to about 50 um, for example, within a range fromabout 10-30 um, such that the layer 110L1 can provide a soft at leastpartially conformable material to receive the lens. The middle layer110L2 can be from about 20 um to about 150 um, for example, and materialM2 can have a modulus greater than first material 110M1 of first layer110L1, so as to deflect the epithelium of the eye when the middle layeris deflected. The third layer 110L3 can be within a range from about 5um to 50 um, for example within a range from about 10 um to about 30 um,and can cover second layer 110L2 so as to retain the second layer in theinner portion 110 of the covering 100.

FIG. 1C2A shows a covering as in FIG. 1C1 placed on the cornea with asmooth upper surface and a lower surface conforming to irregularity ofthe cornea near the edge of the ablation. As the epithelium can be about50 um thick, in many embodiments the dimension 102 is sized so as tocover substantially the ablated cornea for vision correction and smallerthan the ablation zone, such that the outer portion 120 can conform atleast partially to the epithelium. The outer portion 120 may extend tothe sclera, and comprise a tri-curve covering 100 as described herein,with the inner portion 110 having first layer 110L1 of first material110M1, second layer 110L2 of second material 110M2, and third layer110L3 of third material 110M3.

FIG. 1D shows a therapeutic covering 100 comprising a first innermaterial 110M and a second outer material 120M, in which the outerportion 120 comprises a hardness configured to conform with epitheliumof the cornea and in which the inner portion 110 comprises secondhardness configured to smooth the epithelium and conform to the ablatedprofile 20. The outer material 120M may comprise many materials asherein. The Shore A hardness of each of the inner portion and the outerportion can be within a range from about 5 to about 90. For example, theouter material 120M may comprise silicone having a hardness Shore Adurometer parameter from about 20 to about 50, for example from about 20to about 40, and the inner material 110M may comprise silicone having ahardness durometer parameter from about 40 to about 90, for example fromabout 50 to about 90. The outer portion comprises a perimeter 120P, andthe perimeter may comprise a peripheral and circumferential edgestructure to abut the epithelium to form the seal with the epithelium,for example when the base radius of the covering is less than thecornea. The peripheral and circumferential edge structure can be shapedin many ways to define an edge extending around the perimeter to abutthe epithelium, for example with one or more of a taper of the edgeportion extending to the perimeter, a bevel of the edge portionextending to the perimeter or a chamfer of the edge portion extending tothe perimeter. The inner portion 110 may comprise inner thickness andinner material 110M and the outer portion 120 may comprise an outerthickness and outer material 120M, in which the inner thickness issubstantially similar to the outer thickness.

The peripheral edge structure to abut the epithelium can be used withmany configurations of the inner portion as described herein. Forexample, the inner portion may comprise an RGP lens material having alower rigid surface to contact and smooth the cornea and an upper rigidoptical surface. Alternatively, the inner portion may conform to thecornea as described herein. The outer portion may comprise a skirt, andthe skirt may comprise the peripheral edge structure to abut and sealthe cornea, such as the chamfer. The rigidity of the outer portioncomprising the edge structure can be determined to seal the cornea withone or more of hardness and thickness, as described herein.

FIGS. 1E and 1F show top and side views, respectively, of covering 100comprising inner portion 110, outer portion 120, and a peripheral rimportion 140 disposed around outer portion 120. The peripheral portion140 can be more rigid than outer portion 120. Work in relation toembodiments suggests that in some instances the lower sticky tackysurface of outer portion 120 can stick to itself during deployment ontothe eye, and the peripheral portion 140 can improve handling when thecovering is placed on the eye. The covering may comprise a single pieceof material or may comprise multiple pieces adhered together, forexample molded together. For example, the covering may comprise an innerthickness of inner portion 110 and an outer thickness of outer portion120, in which the inner thickness is greater than the outer thickness.The peripheral portion 140 may comprise a thickness, and the thicknessof the peripheral portion 140 can be greater than the thickness of outerportion 120 such that the peripheral portion 140 is more rigid than theouter portion 120. The thickness of the inner portion 110 and thethickness of the peripheral portion 140 can be substantially similar,and these portions may comprise substantially the same thickness andrigidity.

FIG. 1G shows covering 100 comprising inner portion 110 and outerportion 120, such that outer portion 120 comprises a taper 120T ofthickness 108 extending between the perimeter of the inner portion 110and the perimeter of the outer portion 120. The taper may comprise asubstantially linear change in thickness 108 extending between theperimeter of the inner portion and the perimeter of the outer portion.

FIG. 1G1 shows a covering 100 comprising inner portion 110 and an outerportion 120 comprising the taper as in FIG. 1G, and an outer rim orflange 120F of substantially uniform thickness peripheral to the taper120T. The outer taper may extend from the dimension across 102 of theinner portion 110 to the dimension across 154A that is less than thedimension across 104 of the outer portion. The rim of substantiallyuniform thickness may comprise an annular shape having a thicknesswithin a range from about 10 um thick to about 40 um thick, and maycomprise a width 154B within a range from about 0.05 to about 0.8 mm,for example about 0.5 mm. The rim, for example flange 120F, may comprisea thickness of no more than about 50 um, such that the flange comprisesa thickness no more than the epithelium.

The covering 100 can be dimensioned in many ways. The total diameteracross can be from about 6 mm to about 12 mm, for example about 10 mm.The inner portion may comprise a diameter within a range from about 4 mmto 8 mm, for example about 6 mm. The annular rim comprising flange 120Fcan extend around the perimeter of the covering with a thickness ofabout within a range from about 5 um to about 50 um, for example about35 um. The annular rim comprising flange 120F may comprise an innerdiameter of within a range from about 5 mm to about 11 mm, for exampleabout 9 mm and an outer diameter within a range from about 6 mm to about12 mm, for example about 10 mm and corresponding to the perimeter of thecovering. The annular rim may comprise a width of within a range fromabout 0.1 mm to about 1 mm, for example 0.5 mm, extendingcircumferentially around the covering. The outer portion 120 maycomprise the rim with flange 120F and a taper 120T that extended frominner portion 110 to the rim comprising perimeter 120P. The taper inthickness can be substantially uniform between the outer diameter of theinner portion and the inner diameter of the rim, and the boundaries ofthe taper can be rounded and smoothed near the inner portion and therim. The central portion may comprise a substantially uniform thicknesswithin a range from about 50 um to about 150 um, for example 50 um. Thebase radius of curvature of the lower surface of the covering can bewithin a range from about was about 7 mm to about 8 mm. The lowersurface may comprise an aspheric surface or a bicurve surface andcombinations thereof. The upper surface of the covering can comprise aradius of curvature along the inner portion within about 0.1 mmcurvature of the lower surface, such that the covering is substantiallyuniform with no substantial refractive power, for example refractivepower within about +/−1D.

FIGS. 1G1A to 1G1H show a covering as in FIG. 1G1 and dimensionssuitable for use in accordance with embodiments as described herein suchas with experiments, clinical studies and patient treatment. FIG. 1G1Ashows an isometric view of covering 100 having the inner portion 110,the outer portion 120, the taper 120T and rim comprising flange 120F.FIG. 1G1B shows a bottom view of covering 100. FIG. 1G1C shows a sideview of the covering 100. FIG. 1G1D shows a top view of the covering100. FIG. 1G1E shows a side cross sectional view of covering 100 alongsection D. FIG. 1G1F shows detail C of cross-section D-D, including theradius of curvature R1 of the lower surface of the inner portion 110,and the upper radius of curvature Rupper of the inner portion 110. Theupper radius of curvature Rupper may correspond substantially to thelower radius of curvature R1 prior to placement on the eye, for exampleto within about +/−1 D of optical power, such that the inner portion 110prior to placement may comprise no substantial optical power. Detail Cshows a side cross sectional view of covering 100 of the inner portion.FIG. 1G1G shows detail B of cross-section D-D. Detail B shows a sidecross sectional view of the rim comprising flange 120F. The flange 102Fhas a thickness 109. Flange 120F may comprise a taper extending along awidth 102FW, for example from a first thickness 109A of about 35 um tosecond thickness 109B of about 25 um extending along width 120FW nearthe chamfer. Flange 120F comprises a chamfered edge 120FE to contact thecornea or conjunctiva along perimeter 120P of the covering.

FIG. 1H1 shows spatial frequency and elevation smoothing of anepithelial irregularity 12I transferred to a front surface 110U ofcovering 100 as in FIG. 1-2A. The regenerating epithelium 12R comprisesan irregularity 12I. The covering 100 conforms substantially to theshape ablated in the stroma when positioned on the eye as noted above.The covering 100 comprises a rigidity so as to conform substantially tothe ablation profile 20 over about at least about 3 to 4 mm of theablated stroma such that the patient can see and receive opticalcorrection with the ablated surface. The regenerating epitheliumcomprises a thickness profile 12RP that includes irregularity 12I. Theconformable covering comprises a thickness profile of thickness 106 thatencompasses a deformation thickness over the irregularity 106D. Thethickness of the covering can vary over the epithelium to smooth theirregularity transmitted to the front surface of the covering so as toimprove patient vision consistent with the ablation profile 20 when thecovering conforms to the ablation profile 20. For example thickness 106Dover the irregularity can be less than thickness 106 away from theirregularity. The irregularity may comprise an indentation and thecovering may be thinner over the indentation. The silicone elastomer andhydrogel materials as described can be at least somewhat compressible soas to conform at least partially to the cornea and form an indentationso as to receive a portion of the cornea comprising one or more ofepithelium or ablated stroma and decrease aberrations.

Experimental studies of OCT images and Pentacam™ images and topographyimages, noted below, indicate that the thickness of the inner portion ofthe covering 100 can vary so as to decrease optical aberrations alongthe upper surface when the covering is adhered to the cornea. Thisvariation in thickness can be related to one or more of stretching ofthe covering over the irregularity or compression of the covering overthe irregularity.

The irregularities of the epithelium generally comprise spatialfrequencies that are greater than the spatial frequencies of the visioncorrecting portion of the ablation. The covering can provide spatialfiltering of the frequencies of the underlying surface so as to inhibitrelatively higher spatial frequencies of epithelial irregularities andpass relatively lower spatial frequencies corresponding to visioncorrection, such as lower spatial frequencies corresponding to sphereand cylinder. The spatial frequencies ablation profile 20 that areuseful to correction vision can be lower than the spatial frequencies ofthe irregularities, and the spatial dimensions of the vision correctiongreater than the dimensions of the irregularities. For example, thespatial frequencies of the vision correction can correspond to periodsof oscillation less than the periods of oscillation of theirregularities.

FIG. 1H2 shows spatial frequency and elevation smoothing of theepithelial irregularity with a plot of relative height relative for theupper surface of the covering and the upper surface of the irregularity.The irregularity of the regenerating epithelium 12R may comprise aprofile height 12RPH and profile width 12RPW. The upper surface of thecovering may comprise a profile 110UP. The irregularity of the uppersurface corresponding comprises a width 110UPW and a height 110UPH.Height 110UPH is less than height 12RPH so as to correspond to smoothingof the irregularity. Width 110UPW is greater than width 12RPW so as tocorrespond to smoothing of the irregularity. Profile 110UP of the uppersurface of the covering corresponds to lower frequencies than profile12RP, such that the covering comprise a low pass spatial frequencyfilter. This can be seen with the Pentacam™ and topography data shownbelow in conjunction with OCT images showing that the covering andcornea conform without a substantially gap disposed therebetween.Alternatively or in combination, the covering can smooth the cornea whena gap is present, for example when a portion of the cornea is smoothedwith contact to the covering and the gap provides an environment for theepithelium to grow smoothly over the ablation.

Based on the teachings described herein, a person of ordinary skill inthe art can conduct studies to determine empirically the rigidity of theinner portion so as to pass substantially vision correction spatialfrequencies of the ablation to the upper surface of the covering andinhibit spatial frequencies of the irregularities of the ablated stromaand epithelium, for example with Pentacam™ and topography studies asdescribed in the experimental section.

Work in relation to the embodiments as described herein indicates that acovering comprising a modulus within a range from about 4 MPa to about20 MPa can provide smoothing with low pass spatial frequency filteringas described with reference to FIGS. 1H1 and 1H2. The covering maycomprise an elastically stretchable material, for example an elastomeror a hydrogel, such that the lens can conform at least partially to theablated stroma and exert at least some pressure on the ablated stromaand epithelium when at least partially conformed so as to smoothirregularities of the epithelium and irregularities of the stroma. Thecovering can comprise a thickness and a hardness so as to provide thespatial frequency filtering to improve vision in post-PRK patients withthe modulus within the range from about 4 MPa to about 20 MPa. Forexample the lens thickness can be increased to increase the modulus,decreased to decrease the modulus. The hardness of the material can beincreased to increase the modulus and decreased to decrease the modulus.The modulus within the range from about 4 MPa to about 20 MPa canattenuate substantially higher spatial frequencies corresponding toirregularities of the epithelium and stroma so as to smooth the highspatial frequencies corresponding to the irregularities that can degradevision, and can conform substantially to lower spatial frequencies thatcorrespond to the vision correction so as to pass the lower spatialfrequencies corresponding to vision correction so that the patient canexperience an improvement in vision when the epithelium regeneratesunder the covering. For example, the high spatial frequencies maycorrespond to frequencies greater than about ⅙ (0.17) cycles per mm, andthe low spatial frequencies may correspond to frequencies less thanabout ⅙ (0.17) cycles per mm. A person of ordinary skill in the art candetermine the modulus and corresponding spatial frequencies to attenuateand pass, in accordance with the teachings as described herein. Forexample, the modulus of the covering can be measured with known methodsand apparatus to measure the modulus of a contact lens, and measurementswith Pentacam™ images as described herein can be used to determine therelationship of the modulus of the measured lens coverings to smooth ofirregularities, conformation of the lens coverings to the ablation, andvision.

FIG. 1I1 shows an inhibition of transfer of a corneal irregularity to afront surface of a covering, for example one or more of a stromalirregularity or an epithelial irregularity. The front surface of thecovering comprises an optical surface for vision without substantiallytransfer of the irregularity to the front surface of the covering.

FIG. 1I2 shows elevation smoothing of the epithelial irregularity with aplot of height relative to a reference sphere for the upper surface ofthe covering and the upper surface of the irregularity. The plot shows asubstantially spherical front surface of the covering, such that thetransfer of the irregularity to the front surface is inhibited.

FIG. 1I3 shows a thickness profile of the covering as in FIG. 1I2 so asto smooth irregularities transferred to the front surface of thecovering. The thickness profile can vary in response to the underlyingsurface, for example with a decrease in thickness corresponding to anelevation in the surface profile of the cornea.

FIG. 1J1 shows covering 100 having a bicurve profile to fit an ablatedcornea. The bicurve profile may comprise an inner portion having a lowersurface comprising a radius of curvature R1 and an outer portion havingan radius of curvature R1B. The inner portion may comprise a radiusselected to fit approximately the post-ablated cornea, for example towithin about +/−2D. The outer portion may comprise the radius ofcurvature R1B sized to correspond to the outer unablated cornea, forexample to within about +/−2D. The covering may comprise an elasticmaterial with a modulus within a range from about 4 MPa to about 20 MPa,such that the covering can conform at least partially to the cornea andsmooth irregularities of the cornea as described herein. R1 can belonger than RIB, for example with PRK ablation to treat myopia. R1 canbe shorter than R2, for example with PRK ablation to threat hyperopia.

FIG. 1J2 shows covering 100 having an oblate profile to fit an ablatedcornea, for example a cornea ablated for myopia. The covering maycomprise an apical radius of curvature corresponding to R1 near a centerof the covering, and a peripheral radius of curvature, based on theconic constant of the oblate profile of the lower surface of covering100. Alternatively, the lower covering 100 may comprise a prolateellipsoid shape to fit a PRK ablation to treat hyperopia.

FIG. 1J3 shows covering 100 having a tricurve profile to fit sclera andan ablated cornea. The tricurve covering may comprise an inner portionwith an inner lower surface having radius of curvature R1 and an outerportion comprising an outer lower surface having radius of curvatureR1B, as described above. The covering may comprise a third portion 132disposed outside the outer portion and having a third radius ofcurvature R1C sized to fit the sclera and contact the conjunctivadisposed over the sclera. Work in relation to embodiments suggests thatcoupling to the sclera may improve alignment of the lens on the cornea.

The covering 100 having the tricurve profile may comprise dimensionssized to fit the cornea and sclera of the eye 2. The covering 100 havingthe tricurve profile may comprise an inner portion 110 and an outerportion 120 as described herein. The outer portion 120 may comprise thethird scleral portion 1325 having curvature R1C shaped to fit the scleraof the eye, for example shaped so as to contact the conjunctiva of theeye such that the conjunctiva is located between the sclera and thescleral portion 132S. The inner portion 110 may comprise a dimension 102and the outer portion 120 may comprise a dimension 104 as describedherein. The covering 100 may comprise a sag height 105 extending betweenan upper location of the inner portion 110 and the outer boundary ofouter portion 120 shaped to fit the cornea. The third portion 132 maycomprise a dimension across 103.

The dimension 102, the dimension 104 and the dimension 103 can be sizedto the eye based on measurements of the eye. The dimension 103 maycorrespond to an annular region of the sclera extending from the limbusto the outer boundary of the third portion across a distance within arange from about 1 to 4 mm, for example within a range from about 1.5 to2 mm. The size of the limbus of the eye can be measured so as tocorrespond to dimension 104, for example, and can be within a range fromabout 11 to 13 mm. The ablation zone can corresponds to dimension 102,and dimension 102 corresponding to the rigid inner portion can be sizedabout 0.5 to about 2 min less than the dimension across the ablationzone, such that the soft outer portion 120 contacts the eye near theedge of the ablation and the epithelial debridement.

The radius of curvature R1C of portion 132 can be determined so as tofit the eye, and can be within a range from about 12 mm+/−3 mm. Theouter portion can be fit to within about +/−0.5 mm, for example towithin about +/−0.25 mm.

The dimensions of the covering 100 can be determined in many ways, forexample with topography measurements of the cornea and sclera. Thecorneal and scleral topography can be measured with many instruments,such as with the Orbscan™ topography system commercially available fromBausch and Lomb, and the Pentacam™ Scheimpflug camera systemcommercially available from Oculus. The ablation profile can be combinedwith the topography to determine the shape of the eye.

The dimensions of covering 100 can be sized to one or more of the corneaand sclera based on tolerances that may be determined clinically.

The outer portion 120 and the third portion 132 may comprise openingssuch as fenestrations as described herein, for example when the materialcomprises silicone.

The outer portion 120 and third portion 132 may comprise a hydrogelmaterial, for example a silicone hydrogel material, and the innerportion 110 may comprise the rigid material 110M, for example secondlayer 110L2 and second material 110M2 between first layer 110L1 of firstmaterial 110M1 and third layer 110L3 of third material 110M3 asdescribed herein.

As the tricurve covering may couple to the sclera so as to provideenvironment 100E to promote epithelial regeneration withoutsubstantially sealing the cornea, the outer portion 120 of the coveringand the third portion 132 of the covering may comprise substantiallywater permeable material, for example when the inner portion 120comprises the rigid material as described herein.

FIG. 1J4 shows covering 100 having a curved profile to fit sclera and anoblate profile to fit ablated cornea. The covering comprises the innerportion having the lower surface with the oblate profile having radiusof curvature R1 comprising an apical radius of curvature and radius ofcurvature RO, and an outer portion comprising a lower surface havingradius R1C to couple to the sclera as described herein. The apicalradius of curvature may comprise a first radius of curvature and theradius of curvature RO may comprise a second radius of curvaturecorresponding to a conic constant of the oblate profile.

The portions of the coverings as described herein, for example the innerportion and the outer portion, may comprise a junction wherein a firstportion connects with a second portion, and the junction may have themodulus as described herein. The covering may comprise a contact lenshaving a central lens portion having a center stiffness of at leastabout 2 psi*mm2 coupled to an outer lenticular junction portion having alenticular junction stiffness of at least about 5 psi*mm2.

FIG. 1J5 shows a covering 100 having the tricurve profile to fit scleraand the ablated cornea similar to FIG. 1J3. The modulus and thickness ofthe sclera contacting portion can be configured in many ways to fit mayeyes with comfort and so as to resist movement of the inner portion 120.The modulus of sclera coupling portion 132 may be no more than about 5MPa and the thickness no more than about 200 um so as to stretchsubstantially for comfort and resist movement of the inner portion whenthe placed on the sclera.

The dimension 103 of sclera contacting portion 132 may correspond to anannular region of the sclera extending from the limbus to the outerboundary of the third portion across a distance within a range fromabout 1 to 4 mm, such that the dimension 103 can be from about 12 mm toabout 16 mm, for example from about 14 mm to about 16 mm.

The radius of curvature R1C, thickness and modulus of the portion 132can be configured so as to fit the eye to resist movement of innerportion 120 and with comfort. The radius of curvature R1C can be sizedless than the radius of curvature of the sclera and conjunctiva. Forexample, the radius of curvature R1C can be no more than about 10 mm,for example no more than about 9 mm when the curvature of the scleralportion of the eye is at least about 12 mm for example. The thirdrelative rigidity may comprise no more than about 4E-5 Pa*m̂3 so as tostretch substantially for comfort and resist movement of the innerportion when the outer portion is placed on the sclera.

The thickness of the third portion having radius of curvature R1C canvary, for example from a thickness of about 200 um to a tapered edge.The outer portion

FIG. 1J6 shows a tapered edge of the covering having a tricurve profileto fit sclera and an ablated cornea as in FIG. 1J5. The third portion132 may comprise a flange 120F having a narrowing taper extending adistance 120FW to a chamfer 120FE. The chamfer 120FE can be definedalong an outer rim where a first convexly curved lower surface joins asecond convexly curved upper surface. The convex surfaces along theouter rim allow the covering to slide along the conjunctiva and thenarrowing taper permits the third portion of the covering to stretchsubstantially and couple to the sclera and conjunctiva with decreasedresistance for comfort.

The dimensions of the covering 100 can be determined in many ways, forexample with topography measurements of the cornea and sclera. Thecorneal and scleral topography can be measured with many instruments,such as with the Orbscan™ topography system commercially available fromBausch and Lomb, and the Pentacam™ Scheimpflug camera systemcommercially available from Oculus. The ablation profile can be combinedwith the topography to determine the shape of the eye.

FIG. 1K shows covering 100 having inner portion 110 and outer portion120, and fenestrations 100F extending through the thickness of thecovering on the outer portion so as to pass a medicament when the corneais sealed. The medicament may comprise an anesthetic, an analgesic, orother medication, for example. The covering sealed to the cornea caninhibit the egress of the medicament toward the epithelial defect sothat reepithelialization is not delayed. For example, an anesthetic suchas proparacaine, lidocaine can be used to inhibit pain when theepithelium regenerates.

FIG. 1L shows fitting of a covering 100 to a cornea. The covering maycomprise a base curvature, for example first radius of curvature R1 ofinner portion 110 that may correspond to a radius of curvature when thecovering comprises first configuration C1 prior to placement on thecornea. The covering may comprise a second radius of curvature R1B. Theablated cornea may comprise a second radius of curvature R2. The outerunablated portion of the curvature may comprise a corneal radius ofcurvature RC. The second radius of R2 of the outer portion 120 can besized to fit the outer unablated portion of the cornea having radius ofcurvature RC, for example to within about +/−1D corresponding to withinabout +/−0.2 mm for RC of about 8

MM.

The first radius of curvature R1 can be greater than the ablated radiuscurvature R2 such that the curvature of the inner portion of thecovering is less than the curvature of the cornea. As the curvature isinversely related to the radius of curvature, the inner portion 110 hasa curvature less than the curvature of the ablation profile 20 of thecornea when the base radius of curvature R1 of the inner portion isgreater than the radius of curvature R2 of the ablated cornea. Thecovering having substantially uniform thickness as described herein withthe curvature less than the ablated cornea can correct visualaberrations that may be related to epithelial irregularity 12I, forexample so as to correct temporary myopia related to irregularity 12I.

Work in relation to embodiments indicates that environment 100E topromote epithelial regeneration can be enhanced when the curvature ofthe inner portion 110 is less than the curvature of the ablated corneacorresponding to radius R2. The base radius of curvature R1 sizedgreater than the radius of curvature R2 of the ablated profile 20 candefine environment 100E with a concave meniscus profile such thatpressure near the boundary of inner portion 110 is decreased toencourage epithelial migration inward as indicated by arrows 30 andpressure near a center of inner portion 110 is increased so as toinhibit formation of irregularity 12I and provide smooth regeneration ofthe epithelium. For example, the inner portion of the covering can havea curvature corresponding to about 1 to about 2.5 D less optical powerthan the ablated profile 20. This amount of lesser curvature of thecovering can correct temporary myopia related to epithelial irregularity12I and may also smooth the irregularity based on the deflectionpressure as described herein, for example.

While the outer portion 120 can be fit in many ways, the outer portion120 may comprise radius of curvature R1B corresponding to about 0 to 2Dless optical power than the corresponding optical power of the unablatedcornea having curvature RC. For example, the unablated portion of thecornea may have an optical power of about 43D, and the outer portion 120may have a curvature R1B corresponding to about 41 to 43D, such that thecovering is fit on the cornea with a fit ranging from matched to loose.Such fitting can be used with tri-curved coverings as described herein.

The tri-curve and oblate covering profiles as described herein can besized similarly to the bicurve surface so as to provide inner portion110 with a decreased curvature and increased radius of curvaturerelative to ablation profile 20 so as to promote epithelialregeneration. For example inner portion 110 may comprise an increasedapical radius of curvature relative to the radius of curvature of theablation profile 20 of the cornea.

The amount of decreased curvature of inner portion 110 can becharacterized in many ways, for example with Diopters of the cornea andDiopters of the front or back surface of the inner portion of thecovering. In many embodiments the covering may comprise an inner portionhaving radius of curvature R1 that can be about 2 D less than theoptical power of the ablated cornea. For example, when the cornea isablated from about 43D to about 40D, the base radius of curvature R1 ofcovering 100 correspond about 38D, two Diopters flatter than the ablatedcornea so as to provide environment 100E.

The deflectable coverings having the amount of relative rigidity withinthe ranges as described herein can be fit to the ablated cornea in manyways. As the covering deflects, the patient can be fit with a coveringthat can be flatter or steeper than the ablation prior to placement onthe eye, and when the covering is placed on the eye the covering candeflect substantially in response to the shape of the ablation so thatthe patient can see and receive the visual benefit of the ablationprofile.

In many preferred embodiments, the amount of the difference in curvaturebetween the front surface of the ablation profile and the covering priorto placement on the eye can be within a range from about 0 D to about 3D so as to promote vision and epithelial regeneration. For example, thecovering prior to placement with configuration C1 can be flatter thanthe cornea by an amount within a range from about 1 D to about 3 D, andwhen placed on the eye the covering deflects so as to conform at leastpartially to the ablated cornea. The epithelium may comprise a thicknessof about 50 um. The covering prior to placement with configuration C1having a curvature flatter than the cornea can decrease pressure to theepithelium near the edge of the covering as the covering with theflatter curvature may be deflected less when the inner portion conformsto the ablation. The covering prior to placement with configuration C1having a curvature flatter than the cornea can increase pressure to theepithelium along the inner portion of the ablation as the covering maybe deflected less when the inner portion conforms to the ablation.

In many embodiments the inner portion 110 has a substantially uniformthickness and no substantial optical power such that the optical powerof the covering corresponding to the index of refraction of thecovering, the upper surface of the covering, and the lower surface ofthe covering, comprises no more than about +/−1.5D, for example no morethan +/−1D. When the covering having the substantially uniform thicknessis placed on the eye and deflected so as to conform at least partiallyto the ablation and smooth the inner 2-3 mm of the cornea, the coveringcorresponds substantially to the ablation profile such that the patientcan see.

FIG. 1M shows deflection of a portion of a covering in response to anepithelial irregularity so as to smooth the irregularity. Theregenerating epithelium comprises a smoothed regeneration profile 12RPSand a smoothed irregularity 12S. For reference, the regeneration profile12RP without the covering and irregularity 12I without the covering areshown. The covering can smooth the epithelium with pressurecorresponding to deflection of the covering as described when thecovering 100 comprises a second configuration 100C2 as herein.

FIG. 1N shows a test apparatus 190 to measure deflection of a portion ofa lens in response to a load. The test apparatus 190 may comprise arigid support having an aperture 192, such that deflection of thecovering 100 through the aperture 192 can be measured. The aperture 192has a dimension across 194 that can be sized smaller than the dimensionacross inner portion 110, so as to measure a deflection 110D of theinner portion 110 in response to a load 196. The deflection 110D maycomprise a peak deflection, for example a distance. The load 196 maycomprise a point load or a load distributed over an area correspondingto diameter 104, for example a pressure from a gas or liquid on thelower side of the covering. The covering may comprise a firstconfiguration C1 corresponding to the shape of the covering prior toplacement on the eye, and the covering may comprise a secondconfiguration C2 when placed on the eye, and the amounts of force and/orpressure to deflect covering 100 can be determined such that covering100 can be deflected without substantially degrading vision and so as tosmooth the epithelium. For example, the covering may deflect slightly soas to decrease vision no more than about 1 or 2 lines of visual acuityand such that the covering can smooth the epithelium and provideenvironment 100E as described herein.

The modulus and thickness of the covering can be used to determine anamount of relative rigidity of the covering 100, the correspondingamount of force to deflect the covering 100 across a distance, and thecorresponding amount pressure to smooth the epithelium with thedeflected covering as described herein.

The amount of relative rigidity can be determined based on the modulusmultiplied with cube of the thickness. The amount of deflectioncorresponds to the 6^(th) power of the deflected span across thecovering, the modulus, and the cube of the thickness. The approximatelyfourth order relationship of the span to the deflection can allow thecoverings as described herein to conform at least partially to theablation profile within a range from about 4 to 6 mm, and inhibitsubstantially irregularities having diameters of about 3 mm or less, forexample.

The deflection can be approximated with the following equation:

Deflection≈(constant)*(Load*Span̂4)/(Modulus*thicknesŝ3)

The above approximation can be useful to understand the properties ofcovering 100, for example with a substantially uniform thickness of theinner portion. The substantially uniform thickness may comprise athickness that is uniform to within about +/−25%, for example to withinabout +/−10%, such that the covering can conform substantially to atleast a majority of the surface area of an ablation zone and inhibitirregularities over a smaller portion of the ablation zone correspondingto no more than a minority of the surface area of the ablation. In manyembodiments, the covering conforms over an area having diameter of atleast about 4 mm and inhibits irregularities over an area having adiameter of no more than about 4 mm, for example less inhibitsirregularities over an area of no more than about 3 mm. For example,based on the above equations, the deflection is related to the fourthpower of the span, such that for a comparable load, a 2 mm span willhave about 1/16^(th) the deflection of a 4 mm span. Similarly, a 3 mmspan will have a deflection that is about 1/16^(th) the deflection of a6 mm span. As the deflection is related to the cube of the thickness,doubling the thickness can decrease the deflection by about a factor of8. The above approximations can be combined with clinical testing todetermine thicknesses and moduli suitable for incorporation inaccordance with embodiments as described herein.

The equations for deflection of an unsupported circular span of amaterial having a substantially uniform thickness are:

$E_{c} = {{E_{1}\left( \frac{t_{1}}{t_{1} + t_{2}} \right)} + {E_{2}\left( \frac{t_{2}}{t_{1} + t_{2}} \right)}}$  Rigidity = E_(c)(t₁ + t₂)³$y = {\frac{3w\; R^{4}}{16\; {Et}^{3}}\left( {5 + v} \right)\left( {1 - v} \right)}$$w = \frac{y\; 16\; {Et}^{3}}{\left( {5 + v} \right)\left( {1 - v} \right)3\; R^{4}}$

where:W=evenly distributed load over the surface, Pressure (Pa)R=span of unsupported material (m)

E=Young's Modulus (Pa)

t=Thickness (m)v=Poisson's Ratio (unit-less, assumed to be constant among materials)y=Deflection (m)

Equations for deflection is described in Theory and analysis of elasticplates, Junuthula Narasimha Reddy, p. 201 equation 5.3.43 (1999).

Although the above equations describe relative rigidity for asubstantially flat surface, the equations can approximate a curvedsurface and a person of ordinary skill in the art can determine thedeflection load and relative rigidity empirically based on the teachingsdescribed herein, for example with finite element modeling.

TABLE A1 Material, modulus, thickness, relative rigidity Dk/anddeflection load of inner portions of coverings as described herein.Uniform Button Button Flexural Flexural Relative Button ThicknessThickness Modulus Modulus Rigidity Material Material (um) (m) (MPa) (Pa)(Pa * m{circumflex over ( )}3) Dk Dk/t Rigid 250 2.50.E−04 35 350000005.47E−04 600 240 Silicone Rigid 200 2.00.E−04 35 35000000 2.80E−04 600300 Silicone Rigid 150 1.50.E−04 35 35000000 1.18E−04 600 400 SiliconeRigid 100 1.00.E−04 35 35000000 3.50E−05 600 600 Silicone Rigid 505.00.E−05 35 35000000 4.38E−06 600 1200 Silicone Exemplary 293 2.93.E−0420 20000000 5.03E−04 600 205 Silicone Exemplary 272 2.72.E−04 2020000000 4.02E−04 600 221 Silicone Exemplary 250 2.50.E−04 20 200000003.13E−04 600 240 Silicone Exemplary 215 2.15.E−04 20 20000000 1.99E−04600 279 Silicone Exemplary 200 2.00.E−04 20 20000000 1.60E−04 600 300Silicone Exemplary 175 1.75.E−04 20 20000000 1.07E−04 600 343 SiliconeExemplary 150 1.50.E−04 20 20000000 6.75E−05 600 400 Silicone Exemplary100 1.00.E−04 20 20000000 2.00E−05 600 600 Silicone Exemplary 505.00.E−05 20 20000000 2.50E−06 600 1200 Material enflufocon 25 2.50.E−051900 1900000000 2.97E−05 18 72 A (Boston ES) enflufocon A 50 5.00.E−051900 1900000000 2.38E−04 18 36 enflufocon A 150 1.50.E−04 19001900000000 6.41E−03 18 12 hexafocon 25 2.50.E−05 1160 11600000001.81E−05 141 564 B (Boston XO2) hexafocon B 50 5.00.E−05 1160 11600000001.45E−04 141 282 hexafocon B 150 1.50.E−04 1160 1160000000 3.92E−03 14194

As shown in Table A1, an RGP material such as an enflufocon or hexafoconhaving a thickness of about 50 um can have a relative rigidity suitablefor epithelial smoothing and so as to conform at least partially to theablated stroma. The rigid silicone having a modulus of about 20 MPa anda thickness of about 250 um will provide a relative rigidity 3E-4 anddeflection under load similar to the RGP material having a thickness ofabout 50 um and modulus of about 1900 MPa so as to provide a relativerigidity of about 2.4E-4. Commercially available RGP lens materials asshown in Table A1 can be combined in accordance with embodiments asdescribed herein so as to provide covering 100. Based on the teachingsdescribed herein, a person of ordinary skill in the art can determinethe thickness of the covering based on the modulus and the intendedrelative rigidity.

Work in relation to embodiments in accordance with clinical studies asdescribed herein has shown that the inner portion 110 of the covering100 having the relative rigidity of about 3E-4 (3×10⁻⁴ Pa*m̂3) can beeffective so to improve vision and conform at least partially of the eyeso as to provide at least some comfort and improve fitting. Many eyeshave been measured with many coverings and work in relation toembodiments indicates that an inner portion 110 having a relativerigidity within a range from about 1E-4 to about 5E-4 (Pa*m̂3) can allowthe covering to conform to the ablation and smooth the epithelium asdescribed herein. For example, inner portion 110 may a relative rigiditywithin a range from about 2E-4 to about 4E-4, and the eye can be fitaccordingly based on the deflection of the covering 100.

The relative rigidity can be related to the amount of deflection of thecovering 100 on the eye. Work in relation to embodiments indicates thata relative rigidity of inner portion 110 about 3E-4 can deflect about+/−2D when placed on the eye so as to conform to an ablation to withinabout +/−2D across the approximately 5 or 6 mm ablation diameter when aninner diameter of about 2 or 3 mm is smoothed. A covering 100 having arelative rigidity of about 1.5 E-4 can deflect about +/−4D when placedon the eye so as to conform to an ablation to within about +/−4D acrossan approximately 5 or 6 mm diameter when an inner diameter of about 2 or3 mm is smoothed.

The outer portion of the covering may comprise a relatively rigidityless than the inner portion to fit an outer portion of the eye such asan outer portion of the cornea or to fit the sclera when placed on theconjunctiva.

The coverings as described herein may comprise a relative rigiditycorresponding to a range within two or more values of many of thecoverings of Table A1, for example a relative rigidity within a rangefrom about 2.50E-06 to about 6.41E-03 (Pa*m̂3), and two or moreintermediate values for example within a range from about 6.75E-05 toabout 5.47E-04 (Pa*m̂3). Based on the teachings described herein thecovering can have a relative rigidity within one or more of many rangessuch as within a range from about 0.5 E-3 to about 10 E-3 (Pa*m̂3), forexample a range from about 1 E-3 to about 6 E-3, for example. Based onthe teachings described herein, a person of ordinary skill in the artcan conduct clinical studies to determine empirically the thickness andmodulus corresponding to a relative rigidity of the inner portion 110for the covering 100 so as to smooth irregularities and conformsubstantially to the ablation zone.

TABLE A2 Pressure for 5 um deflection at diameters of 3, 4, 5 and 6 mmfor coverings of Table A1. Pressure Required to obtain 5 um ButtonRelative deflection (Pa) Button Thickness Rigidity 3 mm 4 mm 5 mm 6 mmMaterial (um) (Pa * m{circumflex over ( )}3) span span span span Rigid250 5.47E−04 1002.2 317.1 129.9 62.6 Silicone Rigid 200 2.80E−04 513.1162.4 66.5 32.1 Silicone Rigid 150 1.18E−04 216.5 68.5 28.1 13.5Silicone Rigid 100 3.50E−05 64.1 20.3 8.3 4.0 Silicone Rigid 50 4.38E−068.0 2.5 1.0 0.5 Silicone Exemplary 293 5.03E−04 921.9 291.7 119.5 57.6Silicone Exemplary 272 4.02E−04 737.6 233.4 95.6 46.1 Silicone Exemplary250 3.13E−04 572.7 181.2 74.2 35.8 Silicone Exemplary 215 1.99E−04 364.3115.3 47.2 22.8 Silicone Exemplary 200 1.60E−04 293.2 92.8 38.0 18.3Silicone Exemplary 175 1.07E−04 196.4 62.2 25.5 12.3 Silicone Exemplary150 6.75E−05 123.7 39.1 16.0 7.7 Silicone Exemplary 100 2.00E−05 36.711.6 4.8 2.3 Silicone Exemplary 50 2.50E−06 4.6 1.4 0.6 0.3 Siliconeenflufocon 25 2.97E−05 54.4 17.2 7.1 3.4 A (Boston ES) enflufocon A 502.38E−04 435.2 137.7 56.4 27.2 enflufocon A 150 6.41E−03 11751.3 3718.21523.0 734.5 hexafocon 25 1.81E−05 33.2 10.5 4.3 2.1 B (Boston XO2)hexafocon B 50 1.45E−04 265.7 84.1 34.4 16.6 hexafocon B 150 3.92E−037174.5 2270.1 929.8 448.4

The data of Table A1 and A2 show that the pressure to deflect a 3 mmzone a distance of 5 um can be about three times the pressure to deflecta 4 mm zone the distance of 5 um, and about 15 times the pressure todeflect the 6 mm zone the 5 um distance. For example, for the relativerigidity of about 3.13E-4 (Pa*m̂3), the 5 um deflection pressures are572.7, 181.2, 74.2, 35.8 (Pa) for diameters of 3, 4, 5 and 6 mm,respectively, such that the central 3 mm of inner portion 110 canprovide a compressive force to irregularities of about 570 Pa when theinner portion 110 conforms to the ablation across a 6 mm span with apressure of about 35 Pa, for example.

The relative rigidity and deflection pressures can be determined formany coverings based on the teachings described herein, for example forcoverings having a plurality of layers having a plurality of materials.

TABLE A3 Relative Rigidity of Layered Coverings Material 2 (Soft)Composite Material 1 (Rigid) Flexural Composite Relative Total LayeredThickness Modulus Thickness Modulus Thickness Modulus Rigidity ThicknessMaterial (m) (Pa) (m) (Pa) (m) (Pa) (Pa * m{circumflex over ( )}3) 270um Exemplary 2.40E−04 2.00E+07 3.00E−05 2.00E+06 2.70E−04 1.80E+073.54E−04 thick Silicone Shield Soft and 1.35E−04 2.00E+07 1.25E−042.00E+06 2.70E−04 1.13E+07 1.99E−04 Hard are Equal 150 um Exemplary1.20E−04 2.00E+07 3.00E−05 2.00E+06 1.50E−04 1.64E+07 5.54E−05 thickSilicone Shield Soft and 7.50E−05 2.00E+07 7.50E−05 2.00E+06 1.50E−041.10E+07 3.71E−05 Hard w/ Equal thickness

When two or more materials are combined so as to provide two or morelayers, the relative rigidity of each layer can be combined so as todetermine a total composite rigidity. For example, the combined rigiditycan be determined for a covering having first layer 110L1 of firstmaterial, a second layer 110L2 of second material M2 and third layer110L3 of third material 110L3, in which the first and third materialscan be the same material.

A weighted average system can be used to treat the two layers as onematerial. The relative amounts of each material and the moduli of thetwo materials can be combined to determine a composite modulus based onthe weight average of the thickness of each layer. For example, with 90um of 20 Mpa material layer and a 10 um of 5 MPa material layer can becombined so as to determine the composite modulus as

20 MPa*0.9+5 MPa*0.1=18.5 MPa

The equations described herein accommodate many layers of differentmaterials and thicknesses.

Based on the composite modulus, one can multiply the composite modulusby the overall thickness cubed, in the present example 18.5 MPa*100̂3.Although these calculations can be based on approximations, a person ofordinary skill in the art can conduct simulations, for example finiteelement modeling simulations, so as to determine the amount of relativerigidity, pressures and deflection forces and pressures as describedherein.

The index of refraction of one or more layers of covering 100 maycorrespond substantially to the index of refraction of the cornea.

One or more of the materials 110M1, 110M2 or 110M3 may comprise an indexof refraction within a range from about 1.38 to about 1.43 so as tomatch the index of refraction of the cornea to within about +/−0.05. Forexample the materials 110M1 and 110M3 may comprise an opticallytransparent soft silicone elastomer having an index of refraction ofabout 1.41 and the material M2 may comprise an optically transparentrigid silicone elastomer having an index of refraction of about 1.43,for example available from NuSul. Alternatively, material 110M1 andmaterial 110M3 may comprise silicone hydrogel and material 110M2 maysilicone, for example.

While the covering may comprise similar materials such as a more rigidsilicone combined with a softer silicone, the covering may comprisedissimilar materials. For example, and RGP material can be combined witha hydrogel, such as the bicurve or tricurve embodiments as describedherein. The covering can extend at least to the limbus for stability.The RGP material may comprise the second layer 110L2 of the secondmaterial 110M2, for example in accordance with Table A, and the hydrogelmay comprise the first layer 110L1 of the first material 110M1 and thethird layer 110L3 of the third material 110M3. The hydrogel may have anindex of refraction from about 1.38 to about 1.42 so as to match theindex of refraction of the cornea of about 1.377 to within about 0.05and may comprise one or more of HEMA, NVP, GMA, MMA, SiH, TRS, HEMA/NVP,MMA/NVP, HEMA/GMA, or SiH/TRS, commercially available from Vista Optics,UK, for example. The hydrogel comprising HEMA/NVP, MMA/NVP, or HEMA/GMAmay have water content within a range from about 40% to about 70% so asto comprise the index of refraction within the range from about 1.38 toabout 1.43. A water content of about 40% corresponds to an index ofrefraction of about 1.43 and a water content of about 70% corresponds toan index of refraction of about 1.38. The hydrogel comprising SiH/TRSmay comprise water content within a range from about 20% to about 70% soas to comprise the index of refraction within the range from about 1.38to about 1.43. With these SiH hydrogels a water content of about 20%corresponds to an index of refraction of about 1.43 and a water contentof about 70% corresponds to an index of refraction of about 1.38.

Surgical Placement of the Covering

FIG. 2A shows surgical placement of covering 100 on an eye having anepithelial defect with an applicator 200. The applicator 200 comprises asupport 210 to carry the covering 100 and a movable component 230 toadvance the covering onto the cornea with motion 240. The support 210comprises an opening 212 sized to receive the movable component 230. Thesupport 210 may comprise a lower portion 220 to couple to the covering,for example to adhere to the covering, and a handle 214. Coupling 220 ofthe support to the covering can be used to carry the covering foralignment and placement on the cornea. The support may comprise a rigidstructure, for example a rigid annular structure 216, to couple thehandle to the lower portion of the support. The handle 214 may comprisea neck 214N that extends to the rigid annular structure 216.

The movable component 230 can be sized and shaped in many ways toadvance the covering 100 onto the eye with the support 210. For example,the movable component 230 may comprise a disc shape portion of a window232 sized to pass within opening 212. The disc shaped portion of rodcomprising window 232 may comprise a window composed of an opticallytransparent material, for example an optically transparent material suchas one or more of a rigid material, glass, glass fibers, plastic,polyacrylate, polyimide, silicone. Alternatively the movable componentmay comprise an annulus sized to pass within opening to contact thecovering.

The support 210 and the movable component 230 each comprise at least aportion viewable therethrough such that the patient can see a fixationlight and the physician can see at least one structure of the eye toalign the covering with the eye when the covering is positioned on theeye. The covering can be positioned with an operating microscope 202,for example an operating microscope of a commercially laser refractivesurgery system. The operating microscope 202 may comprise an objectivelens 204 and an eyepiece 206 for an operator 207 such as a surgeon toview the eye. A fixation light 208 such as an LED may be positioned onthe operating microscope such that the patient can view the fixationlight and fixate on the light 208 so as to steady the eye.

The handle 214 can be pivoted with a hinge, bearing, or pivot mechanismdisposed between the handle and the support 210 such that the handle 214can pivot away from the operating microscope.

The covering 100 may comprise a marking 100MK to align the covering withthe cornea. Alternatively or in combination, the applicator 200 maycomprise a marking 200MK to align the covering with the cornea. Themarking can be helpful, for example when the covering comprises aninferior rigidity less than a superior rigidity.

FIG. 2A1 shows a surgeon's view of the eye through the applicator as inFIG. 2A. The surgeon can view through opening 212 and window 232 so asto visualize a tissue structure of the eye such as the iris 8 or pupil9. The surgeon may visualize the limbus of the eye, for example with lowmagnification of the microscope. The surgeon can align the structure ofthe eye with a structure of the applicator 200. For example, circularaperture 212 can be aligned with pupil 9.

FIG. 2A2 shows a patient's view of a fixation light through theapplicator as in FIG. 2A. The patient can see the fixation light 208through the covering and the applicator, such that the patient canfixate when the covering is placed on the cornea. Prior to placement ofthe covering over the ablation and epithelial defect, the patient mayobserve haze 208H around the fixation light, for example when thecovering is positioned on cornea without liquid disposed on the surface.Although haze 208H may be present, the patient can fixate sufficientlyfor the surgeon to position the covering over the ablation and pupil.

FIG. 2B shows applicator 200 coupled to covering 100 for placement on acornea as in FIG. 2A. The applicator 200 comprises a lower portion 220to couple the applicator to covering 100. The coupling 222 of theapplicator 200 to the covering 100 can be achieved in many ways, forexample with one or more of adhesion, block adhesion, sticking,interlocking structures, or surface tension.

The coupling 222 of the lower port may comprise block adhesion. Forexample, the lower portion 220 may comprise silicone and the coveringmay comprise silicone. The covering can be placed in contact with thelower portion 220 in the presence of a solvent such as alcohol, and thesolvent evaporated such that the covering 100 is adhered to the lowerportion 220. Similar adhesion can be achieved with a wettable coatingdisposed over the covering 100, as described above. The lower portion220 may comprise a wettable coating to contact the covering.

Work in relation to embodiments suggests that in some instances thelower sticky tacky surface of outer portion 120 can stick to itselfduring deployment onto the eye, and the applicator 200 can improvehandling when the covering 100 is placed on the eye.

The covering used with the applicator may comprise many coverings, forexample a covering as described above, a covering as described in U.S.patent application Ser. No. 12/384, 659, filed Apr. 6, 2009, entitled“Therapeutic Device for Pain Management and Vision”, previouslyincorporated herein by reference, or a commercially available covering,such as a commercially available therapeutic contact lens or acommercially available hybrid lens comprising an RGP inner portion and ahydrogel skirt.

FIG. 2C shows applicator 200 coupled to covering 200 with coupling 222comprising block adhesion and peeling 242 of the covering from theapplicator with movable component 230. The lower portion 220 may contactthe covering 100 with an angle such that the covering peels from thesupport when the movable component is advanced. Such peel can beeffective to remove the covering when the covering is adhered to thesupport.

FIG. 2C1 shows applicator 200 coupled to covering 100 with foam 222F toadhere to the covering to the applicator when dry and application of aliquid 222L to release the covering from the applicator when wet.Alternatively, the foam 222F can couple the applicator 200 covering 100such that the covering can be removed with the movable component 230.

FIG. 2D shows applicator 200 coupled to covering 100 with silicone tosilicone adhesion. The covering lower portion 220 of the support 210 maycomprise silicone and a silicone surface. In particular, lower portion220 may comprise a very smooth ⅜″×¼″ silicone tube stretched over a0.344″ ring or tube. The covering 100 may comprise silicone on the uppersurface in contact with the silicone of the lower portion 220, such thatcovering 100 is adhered to the support with a silicone to siliconeinterface. The silicone to silicone interface can be formed withevaporation of a solvent when the lower portion 222 contacts thecovering, as described above. Handle 214 may comprise machinedAcrylonitrile Butadiene Styrene (ABS). Neck 214N may comprise 14 Gage TW204 tube crimped and spot welded so as to attach handle 214 to annularstructure 216. Annular structure 216 may comprise a 0.344″ ring or a0.344″×0.324″ 304 tube.

FIG. 2D1 shows covering 100 coupled to applicator 200 with silicone tosilicone adhesion and the lower surface of the lower portion 220inclined at an angle.

FIG. 2E shows applicator 200 comprising a rigid component 250 and aflexible component 254. The flexible component 254 may comprise aconcave first configuration to carry the covering 100 and a secondconfiguration to release the covering. The rigid component 250 maycomprise a window 252 of a transparent material. The flexible component254 may comprise a thin transparent sheet of material, for example aflexible diaphragm. The flexible component can be urged downward so asto advance covering 100 downward on to the eye with movement 240.

The rigid component 252 and flexible component 254 may define a chamber253. The chamber 253 can be filled with a fluid such as a gas or aliquid. The handle 214 may comprise a button 256 so as to deliver gas tochamber 253 with movement 258 of the button 256. The fluid may comprisea cooled fluid such as a cooled gas or a cooled liquid so as to cool thecornea and denervate the cornea, for example as described in U.S.Provisional Pat. App. Ser. No. 61/279,612, filed on 23 Oct. 2009,entitled “Corneal Denervation for Treatment of Ocular Pain” (attorneydocket no. 26322A-000300US), the entire disclosure of which isincorporated herein by reference and suitable for combination inaccordance with at least some embodiments of the present invention asdescribed herein.

The chamber 253 can be configured to displace a predetermined quantityof air, for example with a syringe to displace the movable component apredetermined amount toward the cornea. Alternatively or in combination,the handle may comprise a bulb to displace the movable component withmovement of the fluid.

FIG. 2E1 shows coupling of a covering to an applicator as in FIG. 2E.The thin flexible component 254 can extend substantially along covering100. The thin flexible component 254 may comprise a coating to inhibitadherence of the covering to the thin flexible component. The coveringmay be adhered to lower portion 220 with adhesion as described above.

FIG. 2F shows an applicator and a covering as in FIG. 2E with theapplicator in an expanded configuration to position the covering on thecornea. The thin flexible component 254 can expand, for example to aconvex configuration with expansion of chamber 252. The covering 100 canpeel from the lower portion as described above.

FIG. 2G shows an applicator 200 and covering 100 with the covering heldin a channel 260 of the applicator. The channel 260 can be sized toreceive the covering 100, for example with a diameter slightly largerthan the covering.

FIG. 2H shows applicator 200 and covering 100 with the applicatorcomprising an extension 270 to deliver the covering. The extension 270can extend between handle 214 and movable component 230 comprisingwindow 232 as described above. Extension 270 may comprise a flexiblecomponent 272 coupled to the window 232, such that the extension 270 canbe pushed toward the eye so as to move the covering toward the eye withmovement 270.

FIG. 2I shows applicator 200 and covering 100 with the applicatorcomprising a slider 270 to release the covering The slider 270 can beslid toward the eye with movement 284 coupled to window 232 such thatthe covering is moved toward the eye with movement 240.

FIG. 2J shows applicator 200 and covering 100 with the applicatorcomprising a hinge 290 to release the covering. The hinge 290 cancomprise an extension 294 movable about a pivot 292. Motion of extension294 about pivot 292 can advance the movable component 230 comprisingwindow 232 toward the eye with movement 240.

FIG. 2K1 and 2K2 show side and top views, respectively, of applicator200 and covering 100 with the applicator comprising a compressedstructure 296 that is released so as to deliver the covering to thecornea. The compressed structure 296 may comprise many materials, forexample a shape memory material such as nitinol, a spring, a metal,plastic, or a combination thereof. The compressed structure can beconnected to the rigid portion of the support with a trigger structure298 such as a latch, notch, L-connector, keeper or loop, such that thecompressed structure can be released with movement 297 the triggerstructure. The compressed structure comprises a first configuration ofthe movable structure of the applicator 100. The structure 296 can besized such that the patient view of the fixation light for alignment isnot occluded substantially and such that the physician view of thestructure of the eye for placement of the covering on the eye is notoccluded substantially.

FIG. 2K3 shows the applicator as in FIGS. 2K1 and 2K2 with the structure296 in a released second configuration so as to deliver the covering 100to the cornea.

FIG. 3A shows applicator 100 comprising a sliding mechanism 300 andextensions 302 coupled to pads 316 to deliver the covering 100. The pads316 can be connected to covering 100 with coupling 222. The pads 316 canbe spaced apart by a distance such that the patient can view thefixation light between the pads. The extensions 302 extend from pads 316to handle 214 at an oblique angle such that the handle does not occludethe view of the fixation light and surgical view of the alignmentstructures of the eye. The extension 302 may comprise one or more of aflexible material, an elastic material, or a shape memory material suchthat the pads can urge apart when the covering is positioned on thecornea with motion 240. For example, a slider 310 can be retracted witha movement 312 such that pads 316 are urged apart with movement 314 whenthe covering is positioned on the cornea. The pads may comprise aninclined lower surface such that the pads can peel away from thecovering when urged apart.

FIG. 3B shows applicator 100 a spring mechanism 320 comprisingextensions 322 coupled to roller pads 326 to as to deliver the covering100 to the cornea. The roller pads can be coupled to the covering 100with coupling 222 as described above. Alternatively, rollers 326 can beused to smooth the covering on the eye, for example when the covering issubstantially dry. The extensions 322 extend from the handle 214 to therollers 326 and may comprise one or more of a flexible, elastic,resilient or shape memory material such that the rollers can move apartwith separation 240 when positioned on the eye and urged toward thecornea with movement 240. The extensions 222 can extend from the rollersto the handle for a sufficient distance at an oblique angle such thatthe handle does not interfere with patient fixation. The rollers can bespaced apart by a distance such that the rollers do not interferesubstantially with patient fixation and the surgeon's view of thestructures of the eye.

FIG. 3C shows a concave roller pad 326C for use with an applicator 100as in FIG. 3B. Each of the roller plurality of roller pads may compriseconcave roller pad 326C. The concave roller pad can fit the covering onthe cornea, so as to smooth the covering onto the cornea as describedabove.

FIG. 3D shows delivery of a covering to the cornea with the applicatorcomprising rollers as in FIGS. 3B and 3C. The applicator can be coupledto the covering with coupling 222. The movement 240 toward the eye canseparate the rollers 326 with movement 324. The rollers can undergorotational movement 328 when separated with movement 324 so as to smooththe covering.

FIG. 4A shows an applicator 400 comprising a fixation ring 410, and FIG.4B shows a side view of the applicator 400. The applicator 400 maycomprise many of the components of applicator 200, as described above,coupled to fixation structure such as fixation ring 410. The fixationring 410 can be affixed to the rigid portion 216 with extensions 416extending from the rigid portion to the fixation ring. The fixation ringmay comprise teeth 412. The teeth 412 can be sized such that the teethengage the sclera, or the limbus, for example. The covering can becarried with coupling 222. The fixation ring 410 can be sized such thatcovering 100 fits within fixation ring 410. The movable component, forexample window 232, can be moved toward the cornea to deliver thecovering when the fixation ring engages the eye with the rigid portionand coupling 222 positioning the covering on the cornea. The applicator400 can be used with an opaque movable component, for example acompressible foam to contact the covering.

FIG. 5A shows an apparatus 500 comprising covering 100 and applicator200 stored in a substantially dry, sterile compartment 510 of acontainer. The apparatus 500 may comprise a kit. The components andpackaging can be sterilized in many known ways such as e-beam, ethyleneoxide gas, and gamma-ray. The apparatus 500 can be provided to thephysician and opened with the applicator 200 coupled to covering 100,for example adhered to covering 100 and ready for placement on thecornea. The covering may comprise at least an optically transparentportion when dry, and the applicator and covering can be viewabletherethrough when positioned on the cornea as described above.

FIG. 5B shows an apparatus 520 comprising covering 100 and applicator200 stored in a substantially moist, sterile compartment of a container.The apparatus 520 may comprise a kit. The components and packaging canbe sterilized in many known ways such as e-beam, gamma-ray, ethyleneoxide and autoclave. The apparatus 520 can be provided to the physicianand opened with the applicator 200 coupled to covering 100, for exampleadhered to coupled to 100 with support 524 to hold the covering againstthe applicator during shipping, such that the covering an applicator areready for use to place the covering on the cornea. The covering maycomprise at least an optically transparent portion when dry, and theapplicator and covering can be viewable therethrough when positioned onthe cornea as described above.

FIGS. 5B1 and 5B2 shows an apparatus comprising a covering and anapplicator stored in a sterile compartment of a container, in which thecontainer comprises a support surface with the covering disposed thereonin a channel sized to receive the applicator, in accordance withembodiments of the present invention;

FIG. 5B3 shows an applicator with a support coupled to a handle with ajoint 540 disposed between the support and the handle to move the handlewhen the support is coupled to the eye. The joint may comprise a pivot,u-joint and additional articulating structures.

FIG. 5C1 shows an apparatus comprising a removal tool 550. The removaltool 550 may comprise an elongate structure 552 that is graspable by auser, for example a syringe or handle. The elongate structure such asthe syringe may comprise a chamber having an amount of liquid disposedtherein. The removal tool comprises a distal portion 560 having a tip568. The distal portion 560 may comprise components of a known hydrodissection tip modified in accordance with the teachings describedherein. The fluid, for example liquid may 550L, may comprise saline, forexample, or a visco-elastic material. The distal portion 560 maycomprise a first proximal extension 562 and a second distal extension564 with an angle 566 disposed therebetween, so as to define an angleand extend substantially along a plane. The distal portion comprises alumen that extends from the syringe to the tip 568. The cross sectionalperimeter of the area of the tip comprises a long distance dimension568L and a short distance dimension, for example major and minor axes ofan elliptical cross section. The long distance dimension 568L of thecross section extends along a third direction.

The long distance dimension 568L be oriented with respect to the handlesuch that the third long dimension extends along the lower side of thecovering. For example the long distance dimension 568L can extend alongthe lower surface of the covering, when the handle is positioned in asuperior temporal location relative to the eye, such that fluid flowsinferiorly and nasally when the covering is separated from theregenerated epithelium with the liquid.

FIG. 5C2 shows the distal portion 560 of the removal tool. The angle 566can be from about 120 to about 150 degrees, for example 135 degreessimilar to a commercially available hydro-dissection tip for cataractsurgery. The distal portion 560 of the removal tool shown in FIG. 5C2 isangled at 135 degrees with a 11 mm bend to tip.

FIG. 5C3 shows the apparatus of FIG. 5C1 aligned with the patient toposition the tip 568 under the covering. The patient comprises a midlineM and the nose is dispose along the midline. The removal tool 550 can bepositioned on either side of the midline. Alternatively the removal toolmay comprise a first removal tool 550A for positioning on the right sideof the patient and a second removal tool 550B for positioning on theleft side of the patient. The handle of the removal tool can bepositioned oblique to the midline when the tip is positioned under atemporal location of the covering, such that the physician can rest hisor her hand on a support when the tip is positioned under the covering.The long dimension 568L can extend substantially along the plane of thepupil when the tip is positioned under the perimeter of the covering andaligned with the covering for removal and the handle is positioned nearthe temple of the patient. This alignment of the long dimension with thelower side of the covering and the plane of the pupil can decreasedeformation of the epithelium when the covering is removed so as to liftthe covering upward and break the seal to lift the covering upward fromthe cornea. Although, the long dimension 568L can extend perpendicularto the plane of the pupil when the tip is positioned under the perimeterof the covering work in relation to embodiments suggests that suchperpendicular alignment may deflect the epithelium slightly and may notbreak the seal of the covering with the epithelium as effectively.

FIG. 5C4 shows the long dimension 568L of the cross section of theopening of tip 568 aligned substantially with a plane of the pupil and aperipheral temporal portion of the covering when the handle ispositioned near the temple of the patient;

FIG. 5D shows separation of the covering 100 from the regeneratedepithelium 12R with injection of the liquid 550L. The regeneratedepithelium substantially covers ablated profile 20, and may comprise atleast about 2-3 cell layers thick, for example a thickness of at leastabout 20 to 30 um. This substantial covering can occur 2 days or 3 dayspost-op, for example. Work in relation to embodiments suggest that thecovering can remain on the cornea after the initial covering, forexample up to one week post ablation with a high Dk covering providingthe environment to promote reepithelialization as described hereinwithout substantial swelling of the cornea.

FIG. 6 shows a mold 600 to form a covering and having a solid innercomponent comprising a rigid material placed therein prior to injectionof a flowable material. The mold 600 may comprise inner material 110Mpositioned within the mold as a solid piece of material and outermaterial 120M comprising a flowable material injected into mold 600 andcured around the preformed piece comprising inner material 120M. Theflowable material can be injected around the inner material 100M in manyways. For example, the inner material 110M may comprise a second layer110L2 of rigid material 110M2 of the inner portion 110 as describedherein, and the flowable material can be injected around the upper andlower surfaces of second material 110M2 so as to form a first layer110L1 of first material 110M1 and a third layer 110L3 of the thirdmaterial 110M3 with the flowable material such that the first material110M1, the third material 110M3 and the outer material 120M eachcomprise substantially the same soft material when cured. Alternativelyor in combination, the mold may have the first layer 110L1 of the firstmaterial 110M1 and the second layer 110L2 of the second material 110M2placed therein, and the flowable material injected so as to form outermaterial 120M and the third layer 110L3 of the third material 110M3. Forexample, the third layer 110L3 may be formed with a solid spacer ofthird material 110M3 placed in the mold, and the flowable materialcomprising material 110M1 injected around the spacer of cured material110M3 and layer 110M2 so as to form layer.

FIG. 6A shows a mold 600 to form a covering and comprising a solid innercomponent comprising a rigid material placed therein prior to injectionof a flowable material. The mold 600 may comprise inner material 110Mpositioned within the mold as a solid piece of material and outermaterial 120M comprising a flowable material injected into mold 600 andcured around the preformed piece comprising inner material 600. The moldmay comprise an upper portion and a lower portion. In many embodiments,the covering 100 can be formed in a mold with rigid second material110M2 placed in the mold and encapsulated within a single piece ofmaterial comprising first material 110M1, third material 110M3 and outermaterial 120M, such that first material 110M1, third material 110M3 andouter material 120M comprise the same material, for example silicone.The rigid second material 110M2 may comprise silicone bonded to each offirst material 110M1, third material 110M3 and the outer material 120M,for example with curing such that first material 110M1, third material110M3 and outer material 120M comprise the same soft silicone materialbonded to the second material 110M2 comprising rigid silicone.

FIG. 7 shows a method of manufacturing 700 a covering with a mold, forexample as described above. A step 710 provides the mold. A step 715molds the covering to form the covering as described above.

The rigidity and hardness of the molded covering can be determined byone or more of the material hardness, the modulus or the thickness. Themolded covering may comprise a covering with an inner center more rigidthan the outer periphery, for example, and the center can be thickerthan edge. For example, the covering may comprise a single piececovering with an inner portion thicker than the outer portion such thatthe inner portion is more rigid than the outer portion. Alternatively orin combination, an optically clear inner portion can be molded; theinner portion placed in the mold, and the covering molded to form theouter portion around the inner portion. For example, the molded innerportion comprising layer 110L2 of material 110M2 as described herein,and one or more of layers 110L1 or 110L3 molded around layer 110L2. Astep 720 removes covering from the mold. A step 725 coats at least theupper surface of covering with wettable material, and coating of thelower is optional. A step 730 provides the applicator. A step 735couples the applicator to the covering. A step 735 evaporates solvent soas to adhere applicator to covering. A step 740 places the covering andapplicator in packaging. A step 745 sterilizes the contents of thepackage. A step 750 provides the sterile package to physician.

It should be appreciated that the specific steps illustrated in FIG. 7provide a particular method of manufacturing a covering, according to anembodiment of the present invention. Other sequences of steps may alsobe performed according to alternative embodiments. For example,alternative embodiments of the present invention may perform the stepsoutlined above in a different order. Moreover, the individual stepsillustrated in FIG. 7 may include multiple sub-steps that may beperformed in various sequences as appropriate to the individual step.Furthermore, additional steps may be added or removed depending on theparticular applications. One of ordinary skill in the art wouldrecognize many variations, modifications, and alternatives.

FIG. 8 shows a method 800 of placing a covering on a cornea of an eye. Astep 805 provides the sterile package with covering and applicator tophysician. A step 810 treats the cornea to inhibit pain. A step 815debrides the epithelium. A step 820 ablates the cornea. A step 825allows the cornea to dry at least slightly, for example with one or moreof room air, oxygen or a sponge. The cornea may also be dried with airflow from a pressurized source such as oxygen from a canister. A step830 opens the packaging. A step 835 fixates the patient visually on thefixation target with viewing of the fixation target. A step 840positions the covering above cornea in the optical path of the fixationlight when patient views light. A step 845 advances the covering towardcornea with the applicator. A step 850 contacts cornea with thecovering. A step 855 releases the covering from the applicator, forexample ejects covering from the applicator. At step 860, the coveringis adhered to the cornea to seal the cornea, for example with one ormore of a radius of the covering less than the radius of the cornea, asticky tacky lower surface of the covering, a substantially conformableouter portion of the covering to seal the cornea, a rigidity of theperimeter of the covering sufficient to abut the epithelium and seal thecornea, for example with deformation of the epithelium, or a conformableportion of the covering disposed over the boundary of the epithelium andthe debrided region. A step 865 applies one or more of gas, air, oxygen,or sponge, so as to remove bubbles and/or gaps between the cornea andthe covering positioned thereon. At a step 870 a liquid comprisingwater, for example saline, is applied to the covering and when thecovering is sealed on the cornea so as to inhibit swelling. At a step875, the epithelium regenerates over at least a peripheral portion ofthe covering, for example over a perimeter of the covering. Theepithelium may regenerate toward a center of the covering over the uppersurface of the covering. At step 880 the epithelium regenerates along alower side of the covering within the chamber, for example guided by thelower surface of the covering and the ablated PRK surface. A step 885allows the patient to see with the covering in position. At a step 890,the epithelium regenerates substantially across the ablated surface, forexample with a cell layer comprising at least about 2-3 cells across theablated surface. At a step 895, the covering is removed when theepithelium is substantially regenerated. The covering can be removedwhen no substantial visual interference results from removal such thatvision is not substantially changed with removal, for example no morethan one line of visual acuity.

Work in relation to embodiments suggests that the covering can be lefton the cornea with high oxygen permeability for more than a plurality ofdays, for example at least one week, such as one month or more, suchthat the epithelium is substantially regenerated across the ablation toa thickness of at least about 40 um and at least about 4-5 cell layersand so as the covering has guided the regeneration of the epithelial andthus provides a smooth epithelium for vision. For example, the coveringmay remain on the cornea for about one month post PRK ablation to smoothand regenerate the epithelium on the ablation profile with goodadherence of the epithelium to the ablation profile and good patientvision.

It should be appreciated that the specific steps illustrated in FIG. 8provide a particular method of treating a patient, according to anembodiment of the present invention. Other sequences of steps may alsobe performed according to alternative embodiments. For example,alternative embodiments of the present invention may perform the stepsoutlined above in a different order. Moreover, the individual stepsillustrated in FIG. 8 may include multiple sub-steps that may beperformed in various sequences as appropriate to the individual step.Furthermore, additional steps may be added or removed depending on theparticular applications. One of ordinary skill in the art wouldrecognize many variations, modifications, and alternatives.

FIG. 9 shows a method 900 of removing a covering adhered to anepithelium of a patient. A step 905 provides a covering adhered to thecornea of the patient, for example as described above. A step 910anesthetizes the eye with anesthetic, for example numbs the eye. A step915 provides a tool to remove the covering. The tool may comprise anelongate structure having a lumen to extend under the covering and passthe liquid under the covering, for example a hydro-dissection tool. Astep 920 sprays the covering and surrounding area of the cornea withliquid. A step 930 identifies, for example selects, a location of entryunder the covering, for example a point of entry under the covering. Astep 940 identifies and an orientation, for example selects and angeland trajectory, to advance the removal tool inwardly, for example towardthe pupil. A step 950 gently advances the removal tool. A sub-step 952limits the distance the tool is advanced to 1-2 mm. A sub-step 954responds to tactile feedback so as to limit advancement of the toolunder the covering. A step 960 determines when to inject the liquidunder the covering, for example saline. A step 962 determines a quantityof liquid to inject. A step 965 injects the liquid to separate at leastpartially the covering from the substantially regenerated epithelium. Astep 968 lifts the covering when the covering is at least partiallyseparated from the epithelium. The lifting of the covering can identifyfurther separate the covering from the epithelium so as to identifyadherence of the covering to the epithelium, for example locations ofadherence of the covering to the epithelium.

A step 970 completes removal of the covering with separation of thecovering from the substantially regenerated epithelium. A sub-step 972determines locations of covering attachment to the cornea, for examplewhen the covering slips. The covering can be lifted further based on theattachment locations. A sub-step 974 may use forceps to remove thecovering.

A step 980 returns the covering to the supplier for analysis. A sub-step982 determines where and what type of material and/or cells the depositscomprise and whether cells of the epithelium remain attached to thecovering. A sub-step 984 evaluates durability of the covering. Asub-step 986 evaluates the tear break up time (hereinafter “TBUT”) andoxygen (hereinafter “O2”) permeability of the covering.

It should be appreciated that the specific steps illustrated in FIG. 9provide a particular method of removing a covering from a patient,according to an embodiment of the present invention. Other sequences ofsteps may also be performed according to alternative embodiments. Forexample, alternative embodiments of the present invention may performthe steps outlined above in a different order. Moreover, the individualsteps illustrated in FIG. 9 may include multiple sub-steps that may beperformed in various sequences as appropriate to the individual step.Furthermore, additional steps may be added or removed depending on theparticular applications. One of ordinary skill in the art wouldrecognize many variations, modifications, and alternatives.

The method 700, the method 800 and the method 900 can be combined. Forexample a covering can be manufactured in accordance with method 700 andprovided to the physician, the covering placed in accordance with method800, and the covering removed in accordance with the method 900.

EXPERIMENTAL

Based on the teachings described herein, a person of ordinary skill inthe art can conduct experiments and clinical studies to determinesealing of the cornea with the covering to promote epithelialregeneration and improved vision.

Clinical studies to determine smoothing of corneal irregularities withthe covering.

A clinical study was conducted to determine smoothing of cornealirregularities using the covering with dimensions as described abovewith reference to FIGS. 1C1, 1G1A to 1G1H and a rigid inner portion andsofter outer portion as shown with reference to FIGS. 1C1.

The clinical study included images from at least 10 patients that showedconsistent smoothing of the front surface of the covering as compared tothe front surface of the cornea.

FIG. 10A shows corneal topography and smoothing of epithelialirregularities with the covering at 24 hours post-op. The Pentacam™image shows the profile of the front surface of the cornea comprisingthe epithelium, the epithelial defect and ablated stroma. Thecommercially available Pentacam comprises Scheimpflug camera and prismto profile the front surface of the cornea when the covering ispositioned on the cornea. The central portion of the ablated stromaprofile comprises an irregularity referred to as a central island havinga steep curvature corresponding to an optical power of about 46Dsurrounded by flatter portions of the ablated cornea having a curvaturecorresponding to an optical power of about 40D. The EyeSys™ refractivemap comprises a front surface refractive map of the optical power of thecovering when the covering is positioned over the irregularities shownin the Pentacam™ image. The refractive map shows a much smoother surfacehaving a curvature corresponding to a refractive power of about 43D at 3mm, 44D at 5 mm and 44D at 7 mm. Based on these images the front surfaceof the covering is substantially smoother than the underlyingepithelium.

FIGS. 10B, 10C and 10D show horizontal, vertical and central OCT images,respectively, of the covering on the eye of FIG. 10A without a gapdisposed between the covering and the cornea such that the coveringdirectly contacts the ablated stroma and regenerating epithelium. FIGS.10B and 10C show an advance edge of the regenerating epithelium. FIG.10D shows the thickness of the central portion of about 93 um and anablated corneal thickness of about 427 um and 414 um. Each of theseimages show direct contact of the covering to the cornea and no gapappears between the covering and the cornea.

Similar images have been obtained at 48 and 72 hours post-op and showsmoothing of the covering, and that the central island of the corneadecreases with time.

Images similar to 10A to 10D have been obtained and show smoothing witha majority of patients, such that the covering with tear smooth theirregularities of the cornea. The wettable surface coating of the frontsurface can provide a tear on the front surface to smooth irregularitiestransferred to the covering.

Clinical Studies to Seal the Covering on the Cornea.

The clinical studies described herein show sealing of the cornea andsmoothing of the epithelial defects of the study. Based on theembodiments describe herein, a person of ordinary skill in the art canconduct additional studies to determine the rigidity of the outerportion of the covering to facilitate removal and seal the cornea.Additional studies can be conducted to determine the conformability ofthe inner portion to correct vision, for example with the ablated stromaas described above. Additional studies may be conducted so as to improvere-epithelialization rates. Such studies can be conducted separately orin combination, in accordance with the embodiments studied, as describedherein.

A clinical study was conducted to determine the effect of coveringrigidity on sealing of the covering with the cornea and epithelialshaping near the perimeter of the covering. Two sets of coverings wereprepared from silicone resin. Each set was coated with a luminouschemical vapor deposition such that the upper surface comprised awettable surface. The coverings had substantially the same shape inaccordance with the dimensions FIGS. 1G1A to 1G1H. The total diameteracross was about 10 mm. The inner portion comprised a diameter of about6 mm. An annular rim of extended around the perimeter of the coveringwith a thickness of about 35 um. The annular rim comprised an innerdiameter of 9 mm and an outer diameter of 10 mm corresponding to theperimeter of the covering. The annular rim comprised a width of 0.5 mmextending circumferentially around the covering. The outer portioncomprised the rim and a taper that extended from inner portion to therim. The taper in thickness was substantially uniform between the outerdiameter of the inner portion at 6 mm diameter and the inner diameter ofthe rim at 9 mm. The central portion comprised a substantially uniformthickness of about 100 um. The outer rim comprised substantially uniformthickness of about 0.35 um. The base radius of curvature of the lowersurface of the covering was about 7.5 mm. The upper surface of thecovering comprised a radius of curvature of about 7.529 mm, such thatthe covering was substantially uniform with no substantial refractivepower.

The first set of coverings comprised single piece silicone elastomercoverings having Shore A hardness of about 40 (hereinafter “Group I”),for example about 45, and the second set comprised single piece siliconeelastomer coverings having a Shore A hardness of about 85 (hereinafter“Group II”). The Shore A hardness of Group I corresponds to a softcovering, and the Shore A harness of Group II corresponds to a rigidcovering. The covering comprises a shield that protects the cornea. Bothsilicone coverings were coated with an LCVD coating on the upper(anterior) surface and the lower surface comprised a sticky tackysilicone surface to adhere to the cornea.

The OCT images of the eyes show an increased epithelial covering on theperimeter of the corresponding to an inferior location on the eye of thepatient and a decreased covering the perimeter of the coveringsuperiorly. The chamfer abuts the epithelium so as to deflect theepithelium and form an indentation in the epithelium to seal the cornea.The following images are substantially representative and show sealingof the epithelial defect of the cornea following PRK. The hours refersto the hours post-PRK.

FIGS. 11A1A to 11A1D show OCT images of portions of the soft coveringfrom, respectively, the superior portion of the covering, the nasalportion of the covering, the temporal portion of the covering and theinferior portion of the covering at 48 hours post-op on the right eye(OD).

FIGS. 11A2A to 11A2D show OCT images of portions of the soft coveringfrom, respectively, the superior portion of the covering, the nasalportion of the covering, the temporal portion of the covering and theinferior portion of the covering at 48 hours post-op on the left eye(OS).

FIGS. 11A3A to 11A3D show OCT images of portions of the soft coveringfrom, respectively, the superior portion of the covering, the nasalportion of the covering, the temporal portion of the covering and theinferior portion of the covering at 72 hours post-op on the right eye(OD).

FIGS. 12A1A to 12A1C show OCT images of portions of the rigid coveringfrom, respectively, the temporal portion of the covering, the nasalportion of the covering and the inferior portion of the covering at 24hours post-op on the right eye (OD).

FIGS. 12A2A to 12A2D show OCT images of portions of the rigid coveringfrom, respectively, the superior portion of the covering, the temporalportion of the covering, the nasal portion of the covering and theinferior portion of the covering at 48 hours post-op for on the left eye(OS).

FIGS. 12A3A to 12A3D show OCT images of portions of the rigid coveringfrom, respectively, the superior portion of the covering, the temporalportion of the covering, the nasal portion of the covering and theinferior portion of the covering at 72 hours post-op on the left eye(OS).

The soft shields show less covering of the outer portion with theepithelium than the rigid coverings. In some of the above examples withthe rigid shield, the chamfer of the rigid portion extends substantiallyinto the epithelium and may contact Bowman's membrane in at least someinstances. While effective in sealing the covering, work in relation toembodiments suggests that less covering of the outer portion canfacilitate removal.

Additional studies are contemplated to determine the hardness andrigidity to seal the cornea uniformly with hardness parameter that canbe intermediate to those tested as described above. For example,additional studies are contemplated to determine the perimeter suitablefor substantially uniform covering of the epithelium around thecovering, for example with a variable rigidity perimeter as describedabove. Also, studies can be conducted with the coating disposed over thesilicone to determine the promotion of epithelial growth with theenvironment provided high Dk covering and sealing. Work in relation toembodiments indicates that the epithelium of a majority of patients canregenerate substantially within two days post-PRK to cover the ablatedstroma, for example with the LCVD coating on silicone and the shapetested in the embodiments 11A1A to 12A3D. Testing of the oxygenpermeability Dk parameter of these LCVD on silicone embodimentsindicates that the Dk can exceed 400, so as to substantially promoteregeneration of the epithelium.

Clinical Studies of Patients after PRK.

Experimental studies have been conducted to determine the improvement invision with therapeutic coverings as described herein. A series ofpatents was treated with PRK and the patients received a eithercommercially available bandage contact lens (BL) or a therapeuticcovering (TC) as described herein. The study design and protocol was inaccordance with the study designs and protocols described in publishedU.S. patent application Ser. No. 12/384, 659, filed Apr. 6, 2009,entitled “Therapeutic Device for Pain Management and Vision”, the fulldisclosure of which has been previously incorporated by reference andsuitable for combination in accordance with some embodiments of thepresent invention as described herein. The therapeutic covering asdescribed herein comprised molded elastomeric silicone lenses formedwith a mold shaped in accordance with FIGS. 1G to 1G1H above. Theelastomeric lens was treated with LCVD as described herein. The moldedelastomeric silicone lenses comprised a modulus within a range fromabout 4 to about 20 MPa, a Dk of at least about 150, a water content ofno more than about 10%, and a low ion permeability. The clinical resultsare shown in Table I below.

TABLE I Clinical results with therapeutic covering following PRK. %20/40 (6/12) or Better 24 hours 48 hours 72 hours PRK (BL)  25% (n = 24)29% (n = 24)  66% (n = 12) PRK (TC) 100% (n = 13) 92% (n = 13) 100% (n =13)

The data of Table I show patient visual acuity for the patients with thecommercially available bandage lens (BL) and the therapeutic covering(TC) as described herein at 24, 48 and 72 hours, respectively. At alltime points, at least about 92% of the TC patients were 20/40 or better.The TC patient population had 100%, 92% and 100% of patients 20/40 orbetter at 24, 48 and 72 hours post-op, whereas the BL patient populationhad 25%, 29% and 66% of patients 20/40 or better, at 24, 48 and 72 hourspost-op respectively. These data show that the therapeutic covering asdescribed herein can improve visual acuity in individual patients of apopulation of patients having PRK and that the therapeutic coveringprovides better visual acuity for an individual patient than if thepatient had not received the covering. Although the above data wereobtained with a sample size of 24 patients in the BL ground and 13patients in the TC group, additional studies can be undertaken by aperson of ordinary skill in the art, in accordance with the teachingsdescribed herein.

The embodiments as described herein can be combined in many ways. Asused herein like alphanumeric characters describe like structures andmethods and are interchangeable among the figures and supporting text inaccordance with the embodiments described herein.

While the exemplary embodiments have been described in some detail, byway of example and for clarity of understanding, those of skill in theart will recognize that a variety of modifications, adaptations, andchanges may be employed. Hence, the scope of the present inventionshould be limited solely by the appended claims.

1-262. (canceled)
 263. A method of treating an eye of a patient, the eyecomprising a cornea, an epithelium and a sclera, the method comprising:providing a covering comprising: an inner portion having an innerrigidity and at least one inner radius of curvature; and an outerportion having an outer rigidity and at least one outer radius ofcurvature; wherein the inner rigidity is greater than the outerrigidity; and applying the covering against the eye so that the coveringflexes with the inner portion at least partially disposed over andsubstantially conforming to the cornea and with the outer portionengaging the eye along the epithelium, the sclera, or a combinationthereof; wherein, the engagement holds the inner portion on the opticalportion of the cornea; the inner rigidity is from 2.5E-6 Pa-m³ to6.41E-3 Pa-m³; and the outer rigidity is no more than 4E-5 Pa-m³. 264.The method of claim 263, wherein the inner portion comprises a firstcurved portion and the outer portion comprises a second curved portionand a third curved portion; and wherein: the first curved portioncomprises a first lower surface having a first radius of curvature; thesecond curved portion comprises a second lower surface having a secondradius of curvature, and the third curved portion comprises a thirdlower surface having a third radius of curvature; and further comprisinginhibiting movement of the inner portion relative to the optical portionof the cornea by deforming the third curved portion during the applyingof the covering so as to promote motion-inhibiting engagement of thethird lower surface against the sclera of the eye.
 265. The method ofclaim 263, wherein the covering is formed from a material selected fromsilicone, silicone hydrogel, and a combination thereof.
 266. The methodof claim 263, wherein the inner portion comprises a substantiallyuniform thickness; and comprises an index of refraction thatsubstantially corresponds to the index of refraction of the cornea. 267.The method of claim 263, wherein the outer portion is configured tocenter the covering on the cornea.
 268. The method of claim 263, whereinthe inner radius of curvature comprises a radius of curvature less thanthe optical power of the cornea, and further comprising deforming theinner portion during the applying of the covering so that the innerradius of curvature of the inner portion substantially conforms to thecornea.
 269. The method of claim 263, wherein the inner radius ofcurvature is flatter than the cornea by about 1 D to about 3 D, andfurther comprising deforming the inner portion during the applying ofthe covering so that the inner radius of curvature of the inner portionsubstantially conforms to the cornea.
 270. The method of claim 263,wherein treating comprises treating the eye of the patient followingrefractive surgery.
 271. The method of claim 263, wherein treatingcomprises treating the eye of the patient following photorefractivekeratectomy (“PRK”).
 272. The method of claim 263, wherein the patientis in a population of patients, each of the population of patientstreated with the method, and following treatment with the method, atleast about 90% of the population of patients sees 20/40 or betterbetween about 24 hours and 72 hours following PRK.
 273. The method ofclaim 263, wherein treating comprises treating an eye of a patientfollowing laser-assisted in situ keratomileusis (LASIK).
 274. The methodof claim 263, wherein the patient is in a population of refractivesurgery patients after a refractive procedure, and wherein treating theeye of the patient provides a therapy selected from improvingpost-operative visual acuity, reducing the time to restore full visualacuity following refractive surgery, increasing comfort, improvingepithelial healing, reducing edema, reducing light scattering, smoothingthe central 2 mm to 3 mm surface of the cornea, and a combination of anyof the foregoing in the population of refractive surgery patients,compared to a population of refractive surgery patients undergoing asimilar procedure and not wearing the covering.
 275. The method of claim263, wherein when applied to the eye of a patient, the covering sealsthe cornea.
 276. A method of treating an eye of a patient, the eyecomprising a cornea, an epithelium and a sclera, the method comprising:providing a covering comprising: an inner portion having an innerrigidity and at least one inner radius of curvature; and an outerportion having an outer rigidity and at least one outer radius ofcurvature; wherein the inner rigidity is greater than the outerrigidity; and applying the covering against the eye so that the coveringflexes with the inner portion at least partially disposed over andsubstantially conforming to the cornea and with the outer portionengaging the eye along the epithelium, the sclera, or a combinationthereof; wherein the engagement holds the inner portion on the opticalportion of the cornea, wherein the inner portion is characterized by athickness from about 50 μm to about 250 μm.
 277. A method of treating aneye of a patient, the eye comprising a cornea, an epithelium and asclera, the method comprising: providing a covering comprising: an innerportion having an inner rigidity and at least one inner radius ofcurvature; and an outer portion having an outer rigidity and at leastone outer radius of curvature; wherein the inner rigidity is greaterthan the outer rigidity; and applying the covering against the eye sothat the covering flexes with the inner portion at least partiallydisposed over and substantially conforming to the cornea and with theouter portion engaging the eye along the epithelium, the sclera, or acombination thereof; wherein the engagement holds the inner portion onthe optical portion of the cornea, wherein material forming the coveringis characterized by a water content of no more than 1%; an Ionoton IonPermeability Coefficient of no more than about 2.6×10⁻⁶ mm²/min; and anoxygen permeability Dk of 100 or more.
 278. A method of treating an eyeof a patient, the eye comprising a cornea, an epithelium and a sclera,the method comprising: providing a covering comprising: an inner portionhaving an inner rigidity and at least one inner radius of curvature; andan outer portion having an outer rigidity and at least one outer radiusof curvature; wherein the inner rigidity is greater than the outerrigidity; and applying the covering against the eye so that the coveringflexes with the inner portion at least partially disposed over andsubstantially conforming to the cornea and with the outer portionengaging the eye along the epithelium, the sclera, or a combinationthereof; wherein, the engagement holds the inner portion on the opticalportion of the cornea; inner modulus comprises a modulus in a range from1 MPa to 35 MPa; and the outer portion comprises a modulus of no morethan 5 MPa.
 279. A covering for an eye of a patient, the eye comprisinga cornea having an optical portion, an epithelium, and a sclera, thecovering comprising: an inner portion having an inner rigidity and atleast one inner radius of curvature; and an outer portion having anouter rigidity and at least one outer radius of curvature; wherein theinner rigidity is greater than the outer modulus; and wherein thecovering, when applied to the eye, is configured to flex with the innerportion at least partially disposed over and substantially conforming tothe cornea and with the outer portion configured to engage the eye alongthe epithelium, the sclera, or a combination thereof; and wherein, theinner portion is centered on an optical portion of the cornea; the innerportion comprises a modulus from 1 MPa to 35 MPa; and the outer portioncomprises a modulus of no more than 5 MPa.
 280. The covering of claim279, wherein the outer portion is configured to provide engagement withthe eye sufficient to resist movement of the inner portion relative tothe optical portion of the cornea.
 281. The covering of claim 279,wherein the inner portion comprises a first curved portion and the outerportion comprises a second curved and an third curved portion, whereinthe first curved portion comprises a first lower surface having a firstradius of curvature; the second curved portion comprises a second lowersurface having a second radius of curvature; and a third curved portioncomprises a third lower surface having a third radius of curvature;wherein the third curved portion is configured to inhibit movement ofthe inner portion relative to the optical portion of the cornea bydeforming the third curved portion during the applying of the coveringso as to promote motion-inhibiting engagement of the third lower surfaceagainst the sclera, the epithelium, or both the sclera and theepithelium of the eye.
 282. The covering of claim 279, wherein the innerportion comprises a substantially uniform thickness; and comprises anindex of refraction that substantially corresponds to the index ofrefraction of the cornea.
 283. The covering of claim 279, wherein thecovering is formed from a material selected from silicone, siliconehydrogel, and a combination thereof.
 284. The covering of claim 279,wherein the inner portion comprises a radius of curvature less than theoptical power of the cornea, and is configured to deform during theapplication of the covering so that the inner radius of curvature of theinner portion substantially conforms to the cornea.
 285. The covering ofclaim 279, wherein the lower surface of the inner portion comprises anaspherical surface.
 286. A covering for an eye of a patient, the eyecomprising a cornea having an optical portion, an epithelium, and asclera, the covering comprising: an inner portion having an innerrigidity and at least one inner radius of curvature; and an outerportion having an outer rigidity and at least one outer radius ofcurvature; wherein the inner rigidity is greater than the outer modulus;and wherein the covering, when applied to the eye, is configured to flexwith the inner portion at least partially disposed over andsubstantially conforming to the cornea and with the outer portionconfigured to engage the eye along the epithelium, the sclera, or acombination thereof; and wherein, the inner portion is centered on anoptical portion of the cornea; the inner rigidity is from 2.5E-6 Pa-m³to 6.41E-3 Pa-m³; and the outer rigidity is no more than 4E-5 Pa-m³.287. A covering for an eye of a patient, the eye comprising a corneahaving an optical portion, an epithelium, and a sclera, the coveringcomprising: an inner portion having an inner rigidity and at least oneinner radius of curvature; and an outer portion having an outer rigidityand at least one outer radius of curvature; wherein the inner rigidityis greater than the outer modulus; and wherein the covering, whenapplied to the eye, is configured to flex with the inner portion atleast partially disposed over and substantially conforming to the corneaand with the outer portion configured to engage the eye along theepithelium, the sclera, or a combination thereof; and wherein, the innerportion is centered on an optical portion of the cornea; and the innerportion is characterized by a thickness from about 50 μm to about 250μm.
 288. A covering for an eye of a patient, the eye comprising a corneahaving an optical portion, an epithelium, and a sclera, the coveringcomprising: an inner portion having an inner rigidity and at least oneinner radius of curvature; and an outer portion having an outer rigidityand at least one outer radius of curvature; wherein the inner rigidityis greater than the outer modulus; and wherein the covering, whenapplied to the eye, is configured to flex with the inner portion atleast partially disposed over and substantially conforming to the corneaand with the outer portion configured to engage the eye along theepithelium, the sclera, or a combination thereof; and wherein, the innerportion is centered on an optical portion of the cornea; and materialforming the covering is characterized by a water content of no more than1%; an Ionoton Ion Permeability Coefficient of no more than about2.6×10⁻⁶ mm²/min; and an oxygen permeability Dk of 100 or more.